Classification of Organisms
1. GENERAL
This introduction gives only a very general overview of the different organism types. The natural products with
names given in heavy type are only typical representatives of those found. This is particularly true of the prolific
groups such as cyanobacteria and sponges, where this introduction can only give general pointers and should not
attempt to displace the function of the main body of the Dictionary. To obtain a more comprehensive overview of
the natural products present in particular types of organism, it is necessary either (a) to browse the entries given in
the main section of the book, or (b) to search the CD-ROM version. This is most effectively done by using the
Type of Organism codes, which are given in each section below (and above). These can be used alone or combined
with other types of search parameter to restrict the result to certain broad classes of organism.
Many natural products pass up the food chain, and what may have been isolated for example from a sponge,
may in fact be a cyanobacterial metabolite. This phenomenon reflects the large range of signalling roles (in the
widest sense, to include defence chemical and anti-predator substances) that the marine environment involves,
and the complexity of the alimentary chains which leads to frequent metabolic modification of molecules taken
up from prey organisms.
Wherever possible, the Dictionary carries codes for both types of organism in the entry, but this cannot always
be guaranteed. Other marine natural products such as the commoner steroids are just widespread, not necessarily
as part of the food-chain.
Kornprobst, J.-M. (ed.), Substances Naturelles d’Origine Marine, Lavoisier, Paris, 2005
This recent two-volume work gives much background information on all aspects of marine natural products, including
more detailed schemes for correlation of natural product type with taxonomic position of the organism. It was
consulted extensively in preparing this introduction.
Tringali, C. (ed.), Bioactive Compounds from Natural Sources, Taylor & Francis, 2001
2. TAXONOMIC CONSIDERATIONS
The nineteenth century high-level classification of organisms into plant and animal kingdoms has been
abandoned since about the 1960s with the development of cladistic analysis. Since then it has become increasingly
clear that certain groups of organisms, some of them previously little studied, such as the cyanobacteria or
cyanophytes (so-called blue-green algae; more closely related to bacteria), the chromista (including the brown
algae) and the archaebacteria or archaea, show greater differences in both fundamental biochemistry and genetics
from each other and from the so-called higher organisms, than higher plants and animals show from each other.
Whittaker (1959) proposed that the most fundamental division should be between the prokaryotes and the
eukaryotes, a classification that has now been generally accepted, but subsequently modified to include the
discovery of the archaea in the 1970s.
Further studies of the genome might in principle lead to a classification scheme of all organisms that can be
considered ‘absolute’, but many ecologists consider this view as essentially simplistic; for example, it does not
take into account the possibility of convergent evolution in the genome. Evolutionary pressures are exerted
through the phenotype, not the genotype.
Genus names in this Dictionary have, wherever possible, been validated using the Species 2000/ITIS Catalogue of
Life, with which the Chapman & Hall/CRC chemical database has established a reciprocal relationship. The
Catalogue of Life (COL)must be considered the most authoritative resource across thewhole of taxonomy in respect
of taxawhich it currently covers. COL is a cooperative integration and standardisation of the information contained
in many of the world’s authoritative databases. At the time of finalisation of the dataset for this Dictionary, COL
gave a taxonomic view of over half the world’s reported species, and is planned to achieve completion in terms of
published taxa by 2011. Where the name reported in the primary literature is not yet in COL, the genus name was
cross-checked with other internet resources. If a genus name appears unreliable, this is noted in the entry.
ci
There are many different schemes for taxonomic higher-level organisation. The discussion which follows is
largely based on schemes given in Kornprobst (2005). Users should be aware, however, that the classification of
genera into phyla, classes, subclasses, etc. given in Kornprobst is only one view. In some groups of organism (e.g.
molluscs) there is reasonable agreement among biologists; in others (e.g. protozoa) there are huge differences
between different schemes. Since most users of this Dictionary are likely to want to search using broad
parameters (e.g. ‘Find all pyridines in echinoderms’, ‘find all compounds with MW 300-310 in ascomycetes’), the
Type of Organism categories have been kept broad, (largely phyla) and the uncertainties concerning organisation
between the level of phylum and the level of genus should not affect the results. Where there are major taxonomic
uncertainties, as with protozoa, the phylum is not subdivided; all organisms that can reasonably be considered as
protozoa are grouped under the same code heading (ZD). Future development of the database may involve some
further subdivision of these large categories.
Whittaker, R.H., Quart. Rev. Biol., 1959, 34, 210 226 (organism classification )
Cimino, G. et al, Marine Chemical Ecology, (eds. McClintock, J.B. et al ), CRC Press, Boca Raton, 2001, 115
(rev, taxonomy)
2.1 ARCHAEA (Archaebacteria) (ZA)
The archaea are prokaryotic organisms inhabiting extreme environments, both marine and terrestrial, such as
hydrothermal vents, and also highly saline regions. There are three generally recognised groups; thermophiles
(heat-tolerant), halophiles (tolerant of highly saline media such as the Dead Sea; some species are also extremely
alkali tolerant, growing in media up to pH 12) and methanogens (some species of which are also highly
thermotolerant). It is also convenient to recognise a group of ‘psychrophiles’ tolerant of cold arctic and antarctic
conditions. Although only discovered in the 1970s, it now appears that the archaea are in fact the most numerous
bacteria in the marine environment. They show major differences from other prokaryotes in their genome, and
these are carried through into fundamental differences in their membrane structure and biochemistry. Their cell
walls do not contain the glycopeptides found in the eubacteria. Stabilisation of the membrane structure is
affected by esters of glycerol with characteristic branched-chain terpenoid fatty acids, a role which in prokaryotes
is performed by carotenoids and/or hopanoids and in eukaryotes by sterols. Archaeol is considered the prototype
of this type of lipid; there are some unusual structural variations; for example the presence of lipids based on
Calditol is noteworthy. A number of prenylated naphthoquinones related to vitamin K1 have also been isolated,
and sulfur bacteria contain a range of prenylated and aliphatic sulfur compounds.
2.2 EUBACTERIA (ZB)
The eubacteria are characterised by their cell wall structure, which is based on a glycoprotein formed of
(10/4) linked N-acetylglucosamine and N-acetylmuramic acid, cross-linked by peptide side chains containing
unusual amino acids which render different bacterial strains biochemically and immunologically distinct.
In Gram-positive bacteria the glycoprotein coat forms the outermost layer; in Gram-negative bacteria there is an
outer membrane coat which prevents this layer being stained by the reagent.
The classification of bacteria is a complex and specialised subject, and there is no official classification scheme.
The nearest equivalent is the scheme being evolved for Bergey’s Manual (Garrity et al ), which is work in progress
available for inspection online.
Bacteria may be photosynthetic or nonphotosynthetic, and the photosynthetic bacteria may be anaerobic
(sulfur bacteria) or aerobic (which includes the cyanobacteria). The former group utilises the bacteriochlorophylls
as photosynthetic pigments. Further major subdivisions such as alpha, beta-, gamma- and
deltaproteobacteria have been delineated according to various schemes, but the overall picture is complex.
Fortunately, within the context of natural products, the majority of investigations have been into two major
bacterial subcategories, the actinomycetes and the cyanobacteria. The code ZB0001 is used in this Dictionary for
all eubacteria which do not fall into one of these two major groups.
It is possible that some isolations from eubacteria, including actinomycetes, that have not been prominently
flagged in the literature as being of marine origin, do not appear in this Dictionary. To search all bacterial
isolations, consult the Dictionary of Natural Products on DVD. The coverage of cyanophyte products should be
complete.
cii
Lepage, S.P. et al, International Code of Nomenclature of Bacteria, American Soc. for Microbiol, Washington
D.C., 1992
Austin, B., Recent Advances in Marine Biotechnology, (eds. Fingerman, N. et al ), Science Publishers, USA, 2001,
Vol. 6, 1 28 (rev)
Piel, J., Nat. Prod. Rep. , 2004, 21, 519 538 (rev, symbiotic bacteria )
Garrity, G.M. et al, Taxonomic Outline of the Prokaryotes, Bergey’s Manual of Systematic Bacteriology, 2nd edn,
version 5.0, May 2004 http://141.150.157.80/bergeysoutline/outline/bergeysoutline_5_2004.pdf
Moore, B.S., Nat. Prod. Rep., 2005, 22, 580 593 (rev)
Ko¨ nig, G.M. et al, ChemBioChem, 2006, 7, 229 238 (rev, natural products from associated microbes)
2.3 CYANOBACTERIA (ZB1000) (cyanophytes, blue-green algae, Myxophyceae)
The older term blue-green alga is now considered a misnomer, and the cyanobacteria are considered a
subdivision of the photosynthetic eubacteria. They are unicellular organisms which are both marine and
terrestrial; some marine species also inhabit fresh water. Some are truly monocellular, but when found
unassociated with other organisms, many species adhere via their mucilaginous coats into filaments or tufts
visible to the naked eye, and are sometimes found as large colonies known as stromatolites. These are well
documented in the precambrian fossil record and thus place the cyanobacteria among the earliest known
organisms. Schemes for the subclassification of cyanobacteria are based on their mode and degree of such
association, or alternatively by the type of spores formed. Attempts have also been made to classify them
chemotaxonomically. About 7500 species have currently been described. According to one view as few as 200 of
these may be taxonomically distinct, but conversely according to recent chemical studies, a colony appearing to
consist of a single species may comprise many genetically distinct strains. Cyanobacteria are responsible for
frequent algal blooms, the toxicity of which is associated with their high level of secondary metabolites.
Their cell wall structures contain some sterols, but more characteristically conjugated hopanoids such as
Bacteriohopanetetrol. The fundamental chemotaxonomic distinction between prochlorophytes and cyanobacteria
lies in their photosynthetic pigments; in cyanobacteria there is Chlorophyll a but no chlorophyll b, which is
replaced by the phycobilins, Phycoerythrobilin and Phycocyanobilin. These pigments are also found in the red
algae, which show other chemical similarities to the cyanobacteria, notably in their polysaccharides.
Cyanobacteria contain characteristic xanthophylls such as Myxoxanthophyll.
Cyanobacteria are present in the tissues of many sponges, often as a major component of the biomass. In an
extreme case, the species Terpios hoshinota has been characterised as a ‘Cyanobacteriosponge’, in which the
cyanobacterial cell mass constitutes over 50%. Some of the sponge-associated cyanobacteria are of unique type
and have even been assigned to new genera. DNA sequence analysis has shown that different species of Dysidea
sponge are associated with a different cyanobacterium, which may account for the wide range of different
secondary metabolites isolated from them, while mass spectral analysis of colonies of Microcystis and
Planktothrix cyanobacteria has demonstrated the presence in a single colony of multiple strains showing great
diversity in their metabolites. Attempts to separately culture these cyanobacterial cells have proved unsuccessful,
and evidence as to the true origin of the secondary metabolites is based on cell separation experiments. Peptides
such as 13-Demethylisodysidenin and chlorinated diketopiperazines, such as Dihydrodysamide C, were exclusively
found in the cyanobacterial cells, whereas several terpenoids, such as Spirodysin, were found in the sponge cells.
Halogenated aromatics are also associated with the cyanobacterial fraction of Dysidea sponges, and resemble
metabolites such as Ambigols from cultured cyanobacteria.
The most characteristic secondary metabolites of the cyanobacteria, free or associated, however, are
nitrogenous. The known metabolites are also characterised by a high degree of halogenation. See for example the
extensive series of Malyngamides. A high degree of halogenation (notably terminal -CCl3 groups) is shown by
Dysidenin and its relatives isolated from sponge-cyanobacterial symbionts. An extensive series of brominated
indoles typified by the Hapalindoles have been isolated.
Cyanobacteria produce an extensive range of modified depsipeptides, largely cyclic. Examples include the
Lyngbyabellins and Majusculamide C. Acyclic peptides include the Tasiamides and the Microcolins.
Burja, A.M. et al , Tetrahedron, 2001, 57, 9347 9377 (rev )
Gerwick, W.H. et al , Alkaloids, 2001, 57, 75 184 (rev)
Van Wagoner, R.M. et al , Adv, Appl. Microbiol ., 2007, 61, 89 217 (rev)
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2.4 ACTINOMYCETES (ZB5000)
These are a particular class of Gram-positive eubacteria showing filamentous growth, and some similarities to
fungi. (In the past they have often been classified as filamentous fungi and are sometimes called ‘higher bacteria’).
They also merit special treatment biochemically speaking because of their vast production of different types of
natural product, many of them with strong antibiotic or other pharmacological activity. The most important
genera by far in terms of natural products are Streptomyces and Actinomyces; according to which definition is
used, the actinomycetes can also include the important pathogenic genera Nocardia and Mycobacterium.
Actinomycetes occur in marine sediments, and probably as endophytes in many marine organisms, but
evidence is fragmentary. As a group they tolerate a wide range of salinities. A typical situation is that of
the indolocarbazole alkaloids (VX4350), the Staurosporines. Staurosporine itself is produced by various
actinomycetes, both terrestrial and marine, but close homologues have been obtained from ascidians Eudistoma,
from planarians Pseudoceros that prey on them, and from prosiobranch molluscs Coriocella. The Holyrines,
isolated from actinomycetes present in marine sediments, are probable precursors of these compounds and
support the idea that they are all of ultimate actinomycete origin.
Moore, B.S., Nat. Prod. Rep., 2005, 22, 580 593 (microorganism biosynth )
Ko¨ nig, G.M. et al, ChemBioChem, 2006, 7, 229 238 (rev, natural products from associated microbes)
2.5 PROTOZOA (ZD)
The term ‘protozoa’ is difficult to define taxonomically and is subject to ongoing modification in the light of
biochemical studies, which are leading to the reclassification of many groups. It was formerly used as a blanket
term to describe almost any kind of unicellular organism, but it is now known, for example, that the
dinoflagellates (see ZH7000) are more closely related to the brown algae than to other unicellular organisms. In
this Dictionary the code ZD0001 is used for all unicellular organisms that cannot be placed elsewhere*. The
ciliate organisms, for example Paramecium, can be placed here, although it now appears that they are
biochemically closest to the dinoflagellates. It is convenient to recognise four subdivisions; flagellates, amoebae,
sporozoans and ciliates, but the reservations expressed above concerning their fundamental dissimilarities must be
borne in mind, and a proper classification remains premature. Genera studied chemically include Euplotes,
Tetrahymena, Litonotus and Pseudokeronopsis. The ciliates are nonphotosynthetic organisms but can often
harbour photosynthetic algae as symbionts.
Chemical studies have been fairly limited, but a range of sesquiterpenoids, and some highly unusual
triterpenes, the Vannusals, have been isolated.
* Some genera considered dinoflagellates are currently classified in the Dictionary under ZD0001, protozoa,
but they are being reclassified under dinoflagellates, ZH7000, for future releases of the database
3. MARINE ALGAE; GENERAL CONSIDERATIONS
The algae considered in their totality, can be described as lower, mostly multicellular plants of a simple body
plan, lacking well-defined differentiation into roots, stems and leaves. The higher plants, which show such
differentiation, are virtually absent from the oceans, although some species (mangroves; several different spp. of
higher plant) are important components of the estuarine saltmarsh environment.
The classification of algae has undergone a number of changes in recent decades and there is no definitive
overall plan that takes care of every subgroup. The most fundamental division is between the Brown algal branch
and the Green algal branch, two groupings which show large biochemical differences from each other. The
‘Green’ branch comprises not only the green algae proper (Chlorophyta), but also the red algae (Rhodophyta),
which are now considered more closely related to the green algae than either of them are to the brown algae and
their relatives. The taxonomic classification codes used here recognise only these major subdivisions, although
one scheme for the Chlorophyta for example subdivides them into fourteen orders.
Red and brown algae are of commercial significance, but the commercial exploitation of green algae is very
limited. The use of whole plants as food products is mostly confined to Japan, but the extraction of the algal
polysaccharides for use in food and medicines is a major industry.
civ
3.1 CHLOROPHYA (green algae) (ZE)
About 7000 species are recognised, of which 1000 are marine, inhabiting mostly surface waters of the calmer seas.
Of these, about 20% have so far been investigated chemically, principally in the orders Broypsidales and Ulvales.
In their fundamental biochemistry (photosynthetic pigments, storage polysaccharides etc.) they resemble the
higher plants. Some members are unicellular, sometimes as endophytes in other species of green algae.
Green algae photosynthesise using the common carotenoids a- and b-Carotenes, and contain a range of
relatively common xanthophylls such as Lutein. The most common storage polysaccharides are amylose and
amylopectin, and the commonest structural polysaccharide is cellulose, although some groups also secrete b-1,3-
xylan and b-1,4-mannan. The most widespread sterols are Cholesterol, Brassicasterol, Sitosterol and their close
relatives, although some rarer sterols such as Saringosterol have been characterised from certain classes of green
algae. Studies have not always distinguished between sterols involved in the algal membrane structure and those
present in the cytoplasm.
The known secondary metabolites of the green algae are rather limited in structural range and are mostly
confined to terpenoids of relatively common skeleton, and a range of aromatics including meroterpenoids.
Halogenation is uncommon, and the terpenoids are so far limited to sesqui- and diterpenes and a few triterpenes
(acyclic and pentacyclic cycloartanes, e.g. Capisterone B). Many of the terpenoids contain enoloid functionality,
for example Caulerpenyne and/or furan rings formed biogenetically by the cyclisation of the related unsaturated
aldehydes, such as Furocaulerpin. Some of these metabolites have also been isolated from species that feed on
green algae, such as molluscs. Halimedatrial is the only terpenoid so far isolated from green algae containing a
carbon skeleton that has not been found elsewhere. The brominated aromatics are exemplified by Rawsonol, and
the meroterpenoids by Cymopol and related compounds.
Nitrogenous compounds found in green algae tend to be low molecular-weight amines related to the amino
acids, such as Agmatine, or peptides and modified peptides such as the Kahalalides. There are few more highly
elaborated alkaloids except for purines and an unusual 1,3,5-triazine, Halimedin. Exceptions to this generalisation
are the five-ring nitrogenous pigments Caulerpin and Caulersin isolated from the structurally atypical algae of the
Caulerpa genus.
3.2 RHODOPHYTA (red algae) (ZF)
The red algae are characterised by a unique and complex reproductive cycle involving three alternating
generations. The great majority of the 4000 species known are marine, sometimes inhabiting deep water. They
may be mono- or multicellular with a complete absence of flagellae. The chloroplasts have a double membrane
similar to those of cyanobacteria and presumably arose by endosymbiosis with these organisms. There is no
general agreement about the subclassification of red algae. Several schemes have been suggested, and the
taxonomy is fluid, for example the genus Plocamium has now been moved to a separate order, the Plocamiales.
At the highest level, a division into two unequal subclasses is usually recognised. The Bangiophyceae, considered
the more primitive group, is the smaller and consists of either unicellular or very simple multicellular organisms.
The most studied genus chemically in the Bangiophyceae is Porphyra. The larger subgroup is the
Florideophyceae, comprising the better-known more highly differentiated macroscopic plants.
An important biochemical similarity between the red algae and the cyanobacteria is the presence of the
phycobilins, Phycocyanobilin (blue-green) and Phycoerythrobilin (red). It is the latter that is responsible for the red
colour of the tissues, but the colour may be modified or masked by the presence of phycocyanobilin and/or
chlorophylls. The red algae contain chlorophyll a and the characteristic pigment Chlorophyll d. The isolation of
Isochlorin e4 from Dasya pedicellata is also noteworthy. The range of carotenoids is rather limited but includes the
furanoid cyclised xanthophylls Aurochrome and Auroxanthin which are also widespread in terrestrial plants.
The storage saccharides consist not only of highly branched amylopectins but of the osmoregulatory
galactoglycerols Floridoside and Isofloridoside. There is some cellulose content but the most abundant and
characteristic polysaccharides are the commercially significant Carrageenan and Agar. These are rarely present in
the same species. Red algae have a relatively high content of polyunsaturated fatty acids and phospholipids, as
well as some unusual acids such as the cyclopentanoid Dihydrochaulmoogric acid. Derived from these unsaturated
C18 and C20 acids are a large number of oxylipins, for example the Constanolactones and Peyssonenynes.
The range of sterols so far characterised is rather narrow and confined to relatively simple hydroxylated
cholestanes such as the Liagosterols and Pinnasterol. Side-chain methylated steroids are rare; see 11,20-
Dihydroxy-23-methylcholesta-1,22-dien-7-one.
The secondary metabolites of the red algae are characterised by a high proportion of halogenated terpenoids
and aromatics, particularly in the intensively studied genus Laurencia. The terpene skeletons are strongly
cv
weighted towards the lower MW members of the series (especially sesquiterpenes), and there are many
representatives of unique terpene skeletons not found in higher plants or elsewhere in the algae. Kornprobst
[Kornprobst, 2005; 1, 329] attempts a correlation of natural products with taxonomic subgroup (order), but in
view of the taxonomic uncertainties referred to above and to the fact that several groups have hardly been
investigated chemically, this must be considered tentative; the classification of red algae into orders given by
Kornprobst and given here does not correspond with that found in the Catalogue of Life. The Ceramiales (e.g.
Ceramium, Delesseria, Chondria, Laurencia, Polysiphonia) contain many halogenated sesquiterpenes and
brominated aromatics, plus a range of halogenated C15 acetogenins which are characteristic of the order. The
Gigartinales (e.g. Chondrococcus, Plocamium, Ochtodes, Sphaerococcus) also contain many halogenated
terpenes, mostly monoterpenes such as Halomon and Violacene but in the case of Sphaerococcus some (often
brominated) diterpenes based on sphaerane, presphaerane and related carbon skeletons, such as Sphaerococcenol
A and Presphaerol. On the other hand, the Nemaliales (e.g. Asparagopsis, Bonnemaisonia, Rhodymenia ) and
others yield halogenated aliphatic compounds of low molecular weight such as halogenated acetones. The genus
Ochtodes (Cryptonemiales) yielded a range of halogenated monoterpenoids based on the unusual ochtodane
skeleton, such as Ochtodene; other genera in this order did not contain terpenoids. Other orders have either not
been extensively investigated, or yielded only a limited range of natural products.
The order Ceramiales, especially the genus Laurencia, is a rich source of natural products with over 500
compounds so far isolated. The sesquiterpenes of Laurencia are based on more than 20 different carbon
skeletons, some of them ‘traditional’ and found also terrestrial organisms, others novel. Many of these have also
been isolated from molluscs and other animals that feed on red algae. Using chemotaxonomic evidence, the
species in this genus can in fact be divided into three subgenera. The first group contains only halogenated
terpenes, the second only acetogenins and the third group both. However, the situation is complex and there may
be interbreeding between different chemotypes. [Kornprobst 2005; 1, 346 347]. There is also a wide range of
halogenated (mostly brominated) diterpenes, many derived from the common (marine and terrestrial) skeleton
labdane and other skeletons closely related to it. The parguerane skeleton, as found in Parguerene and related
compounds, is however unique to marine organisms. There is also a series of Irieols based on the irieane skeleton.
Certain Laurencia and Chondria species have also yielded a series of triterpenoid polyethers derived from
squalene, for example Thyrsiferol, Enshuol and the Armatols.
The most characteristic class of natural product isolated from these genera, however, is the extensive series of
mostly halogenated compounds based on a linear C15 skeleton, the first of which to be discovered was Laurencin in
1968. A wide variety of structure based on ether formations is founded on this basic skeleton (for example
Obtusenyne; Microcladallenes), which probably arise by loss of a C1 fragment from a C16 precursor. The isolation of
Laurediol supports this hypothesis. The Ceramiales also contain a range of halogenated phenolics such as Lanosol.
Nitrogenous natural products are relatively scarce in the majority of red algae, and mostly limited to widelydistributed
small molecules such as Homarine, and cyclic peptides such as Ceratospongamide (isolated from a red
algal-sponge symbiont). A range of simple halogenated indoles was isolated from Rhodophyllis membranacea.
Once again, it is the Ceramiales that show a much greater range. A characteristic amino acid is Kainic acid,
together with its homologue Domoic acid and other analogues. The range of indoloids is also greater, including
some of greater elaboration such as the Almazoles.
The chemotaxonomic unpredictability of this group of organisms is shown by studies of Chondria californica,
which yielded a range of polysulfur compounds such as Lenthionine. These were unaccompanied by terpenes, and
were not found in apparently closely related species.
3.3 PHAEOPHYTA (brown algae) (ZH1000)
About 1500 species of brown algae are known, almost exclusively marine. The term Phaeophyta is to be
preferred, since modern studies have shown that they are only very distantly related to the other algae and the
term ‘brown alga’ is therefore a misnomer, although it remains in widespread use. Together with the diatoms and
the chrysophytes, they constitute the Stramenopiles. Whereas the other two subgroups are entirely monocellular,
the vast majority of brown algae are multicellular and macroscopic, sometimes attaining very large size. Most
species inhabit cold and temperate, often rough, seas, and are sessile, demonstrating a well-defined differentiation
into a foot (holdfast), stem (stipe) and frond, and growing in surface or relatively shallow waters. The exception
is the brown algae of the Sargasso Sea, which are two free-floating Sargassum species inhabiting tropical waters.
Two superorders are recognised, based on life-cycle criteria. The Fucales do not show generational
alternation, producing haploid gametes which reproduce the diploid stage (cf. higher plants and animals). The
other brown algae show generational alternation between a haploid gametophyte and a diploid sporophyte (cf.
cvi
ferns). In some families the two forms are both macroscopic and may be indistinguishable to the naked eye; in
others, the gametophyte is microscopic. Kornprobst [Kornprobst, 2005; 1, 420 421; ibid ., 481] gives a
classification scheme into 11 orders (the Fucales being one), but as with the red algae, there have been several
different views of the taxonomy in recent years, with much ongoing research having chemotaxonomic
implications. For example, it has been shown that the much-studied Dictyota dichotoma must be considered a
complex in which several endophytic species can be distinguished.
The photosynthetic pigments of all organisms of the Stramenopiles are Chlorophylls a, c1 and c2.
(characteristic absence of chlorophyll b). The carotenoid content is limited to Fucoxanthin and lesser amounts
of Violaxanthin; Diatoxanthin and Diadinoxanthins have also been reported, but may be the result of
diatomaceous contamination of samples. Some Fucales have yielded pseudomonoterpenoids related to Loliolide,
which in other types of organism are known to be degradation products of xanthophylls.
Both the structural and the storage carbohydrates of the phaeophytes differ from those present in other classes
of algae. The main storage polysaccharide is Laminarin, accompanied by Mannitol and Laminitol which perform
osmoregulatory functions. The matrix polysaccharides are based on Alginic acid in which the anions are
carboxylate groups rather than the sulfates found in carageenans and agar. Phaeophytes in the orders Fucales and
Laminariales also contain smaller amounts of the pharmacologically interesting Fucoidin.
As in the red algae, the range of sterols found is limited and mostly based on minor modifications of the
Fucosterol structure, which is the major steroid. There is a wide range of unusual oxylipins, for example the rare
oxa compounds given in the entry for 12-Hydroxy-6,9,11-dodecatrienoic acid, bridged epoxy compounds such as
the Cymathere ethers, and prostanoid-like cyclopentanoids such as the Ecklonialactones.
Brown algae contain a wide range of terpenoids, phenolics and meroterpenoids, but a striking and somewhat
unexpected feature is the paucity of halogenated compounds, and those that are found in small amounts are
bromo- and iodo-, rather than chloro-substituted. They are unique in their ability to concentrate iodine (and also
arsenic; see below) to concentrations of up to 1% dry weight, and although 99% of the iodine in the tissues is
inorganic, the other 1% finds its way into Thyroxine and other iodinated tyrosines, and a small number of
miscellaneous phenolics. There are also few alkaloids, nitrogen compounds being represented only by compounds
of low molecular weight, some peptides such as Fastigiatine and one or two other compounds such as the
terpenoid amide Joalin. However, studies have so far been confined to two orders, the commercially important
Fucales and the Dictyotales. No lower terpenoids have been isolated from the former group, and mostly only
linear diterpenes such as Crinitol, although the presence of the rare cyclobutanoid norditerpene 1-(2-Isopropyl-1-
methylcyclobutyl)-4-methyl-4-nonene-1,8-dione in Cystophora moniliformis is noteworthy. On the other hand the
Dictyotales contain some sesquiterpenes such as Zonarene.
The diterpenoids of the Dictyotales include many examples of prenylogues of well-known sesquiterpenoid
skeletons, for example Dilophol (prenylgermacrane), Dictyotin A (prenylcadinane = biflorane) Dictyotetraene (a
dictyotane) and other elaborations on this theme (for a tabulation in chart form, see Kornprobst, 2005, 1, 442-3).
Other characteristic skeletons are xenicane and its relatives (pachydictyane, crenulane and others), and
dolabellane and dolastane.
The major secondary metabolite content of brown algae is represented by phenols and phenolic
meroterpenoids, many of them sulfated and/or halogenated. The content of these in the tissues may reach
20% by weight and they may play a role in the prevention of larval fixation by marine animals and for protection
against bacteria. A major series is represented by the phlorotannins (see for example Trifucol, Trifuhalols, Eckol
and their numerous homologues) which are radical-induced oligomers of Phlorotannin containing C-C or C-O-C
linkages. The genus Cytoseira has been much investigated and has yielded a large range of structurally diverse
meroterpenoids; for example, Strictaketal, the Cystoseirols and the Mediterraneols.
The reproductive cycle of brown algae is mediated by a range of hydrocarbon pheromones secreted by the
female gametes, and which act as attractants for the male cells. In some orders of brown algae the gametes are
both mobile and may be either of similar (microscopic) size, or with the female gamete larger. The most advanced
form of reproduction is shown by the Fucales, where the female gamete is large and immobile, and the male
gamete is attracted to it solely by the very low concentrations (nanomolar to picomolar) of the attractants. These
molecules modulate the navigation of the male gametophytes in the marine environment over the very short
ranges ( /1mm) required for fertilisation. They are small, non-halogenated aliphatic molecules, the secretion of
which is a unique feature of phaeophyte biochemistry. The majority are C11 compounds which appear to be
derived by degradation of unsaturated acids such as eicosahexaenoic, of a type not found in terrestrial plants.
They may be acyclic (e.g. Cystophorene) or containing 3-, 5-, 6-, 7- or 8-membered rings (e.g. Dictyopterenes A-B,
Multifidene, Aucantene, Ectocarpene and 7-(1-Propenyl)-1,4-cyclooctadiene respectively). Some Fucus and
cvii
Sargassum species employ the smaller molecule 1,3,5-Octatriene (various stereoisomers). Unexpectedly,
Ectocarpene was also found in terrestrial Sencecio spp.
The tissues of brown algae uniquely concentrate inorganic arsenic at concentrations of up to 40ppm and some
of this is converted via biomethylation to dimethylarsinate and thence into a range of ribosides such as 2,3-
Dihydroxypropyl[5-deoxy-5-(dimethylarsino)]ribofuranoside.
3.4 BACILLARIOPHYTES (diatoms), CHRYSOPHYTES (golden algae) and HAPTOPHYTES (ZH5000)
These three groups of unicellular organisms belong to the ‘brown’ major biochemical line and together with the
brown algae (mostly multicellular) constitute the Stramenopiles. The term ‘algae’ formerly applied to some of
these groups is now considered on biochemical and submicrostructural studies to be a misnomer (cf. brown
algae). Although these organism types are linked together in the classification scheme used here, this is tentative
as they may be rather unrelated and biochemically distinct.
These organisms have been relatively little studied chemically by comparison with the brown algae. The
diatoms and haptophytes secrete hard exoskeletons of aluminosilicates and calcium salts respectively, while the
golden algae do not, though they may contain silica microspicules. There are roughly 200 known species of
marine golden algae and 500 of haptophytes, but the number of marine diatom species may be as high at 50,000,
constituting the bulk of the phytoplankton at certain times of the year, and therefore of crucial importance to
marine ecosystems.
The storage polysaccharide of diatoms and Chrysophyceae is Chrysolaminarin. Photosynthetic pigments
resemble those of the brown algae, with no phycobilins but with chlorophylls c including the more recently
discovered Chlorophyll c3. A number of minor xanthophylls have been detected and Phaeodactylum triconutum
has yielded some degraded carotenoids such as Apo-13?-fucoxanthinone. There have been extensive studies on
their lipids on account of their biotechnological importance (cf. algae). The content of sulfur glycerides, especially
1,2-Diacylglycerol 6-sulfoquinovosides (also found in other classes of organism) is relatively high. The range of
known steroids resembles that of the brown algae in being based on limited side-chain modification of the
cholestane skeleton, up to C30 in the case of 24-Propylidenecholesterol, with some sulfation, e.g. Hymenosulfate.
The Bacillariolides appear to be oxylipins produced by the arachidonate pathway. The Prymnesins are toxic
polyethers produced by a haptophyte.
The range of terpenoids isolated is very narrow and limited so far to simple phytanes. It is noteworthy that in
two studied diatom species, the biosynthesis of these (in the chloroplasts) is by a non-mevalonate pathway while
the steroids, produced in the cytoplasm, are mevalonate-derived.
Nitrogenous compounds are similarly few in number, but the toxic pyrrolidine Domoic acid, also found in red
algae, was isolated as a shellfish toxin resulting from Nitzschia infection.
Moore, B.S., Nat. Prod. Rep., 2005, 22, 580 593 (diatoms)
3.5 DINOFLAGELLATES (ZH7000)
Note; Many shellfish toxins are now known to be dinoflagellate metabolites but may not currently be classified as
such in the database
These monocellular organisms are economically important as the causative agents of toxic ‘red tides’.
Biochemical and other studies have shown clearly that they are more closely related to the ciliates and to certain
other groups than they are to other flagellate organisms. (Kornprobst 2005 describes them as ‘Mesocaryotic’, i.e.
intermediate between the eukaryotes and the Stramenopiles). About 200 species are known, predominately
marine. Only just over half are photosynthetic; some are carnivorous. Their main anatomical characteristic is the
possession of two flagellae, one equatorial and one longitudinal. Most are unicellular but some are filamentous.
They participate in a range of symbiotic associations, especially with corals and with molluscs.
Those organisms which are photosynthetic contain chlorophylls a and c. They contain a range of xanthophylls,
most characteristically the C37 trisnortriterpenoid pigment Peridinin and also the structurally unusual
Gyroxanthin. The characteristic steroids are a range of 4a- methyl compounds such as Amphisterol and
Peridinosterol representing an intermediate stage between the tetracyclic triterpenoids and the cholestane/
ergostane type predominant in the brown algae and relatives. Gorgosterol, originally isolated from a gorgonian,
was found later to be produced by a dinoflagellate symbiont.
The known toxins of dinoflagellates fall into two main groups, though the exact type of toxin produced is
genus-specific. The first main group is polyketide-derived, either long-chain with some cyclic ether formation
cviii
(Amphidinols, Luteophanols, Colopsinols, Zooxanthellatoxins) or with multiple ether rings (‘polyether ladders’)
(Brevetoxins, Ciguatoxins, Yessotoxin and their analogues, together with the giant C164 molecule Maitotoxin).
Another structural subtype is shown by Okadaic acid, while other polyketides are macrolides such as the
Amphidinolides. The Prorocentrolides, Pinnatoxins and Spirolides are cyclic nitrogenous polyketides which have
been isolated from shellfish but are known to be dinoflagellate produced. It is notable that in known cases the
biosynthesis of polyketides in dinoflagellates is by a totally different pathway from that in other organisms.
The other main class is composed of nitrogenous guanidinoid toxins of which Saxitoxin is the prototype.
Moore, B.S., Nat. Prod. Rep., 2005, 22, 580 593
3.6 FUNGI (ZG)
Fungi are now considered part of the Eukaryote kingdom, and are characterised by the lack of a photosynthetic
mechanism and by a mode of life which is saprophytic, parasitic or symbiotic. Another major biochemical
difference from algae lies in their cell wall structure usually based on chitin rather than cellulose. Fungi are found
throughout a wide range of terrestrial and marine environments and it is not possible to produce a meaningful
definition of ‘marine fungi’, only to refer to a range of halotolerance among the various fungal species that are
widely distributed. Thus marine sediments and marine invertebrate tissues yield fungal species from genera also
found terrestrially, but which have developed a preference for growing in saline environments. Of the
approximately 100,000 fungal species so far described, about 500 have been found in marine environments, but
this figure is certain to increase in the light of further research. Many metabolites, such as Gliotoxin, have been
isolated from both terrestrial and marine fungi, and when the identical compound has not yet been found in a
terrestrial fungus, there are often close relatives. One basidiomycete species, Coriolus consors (preferred name
Irpex consors ) has been cultivated in both seawater and freshwater and yielded the same natural products. Since
fungi are invariably cultivated on a medium which is then extracted, cross-contamination of cultures by terrestrial
fungi or bacteria is a possibility that must be guarded against.
The lower fungi or Chytridiomycotes (ZG1000) are found only to a very limited extent. They are
taxonomically difficult to classify, resembling the higher fungi in their lack of photosynthesis, but resembling the
monocellular algae in having a cellulosic cell wall structure and a flagellate stage, sometimes with alternation of
generations. There are different views as to how they should classified vis-a` -vis the simpler Stramenopiles, and
several classes of organisms formerly considered to be lower fungi have now been reclassified on biochemical
grounds. Chemical studies are limited.
The majority of fungi fall into the category of higher fungi or Eumycetes having typical fungal biochemistry,
and which can be subdivided into the four main classes of Zygomycetes (ZG2000), Ascomycetes (ZG3000),
Basidiomycetes (ZG4000) and Deuteromycetes (ZG5000). These groups are distinguished by their method of
spore formation (zygospores, asci and basidia respectively for the first three groups). The Deuteromycetes are an
ill-defined group roughly corresponding with the term fungi imperfecti (the terms Mycelia sterilia and
Hyphomycetes are also found according to various schemes). These are fungi in which no reproduction is
observable and which are therefore extremely difficult to identify. Spore formation can be induced in some of
them under laboratory conditions, work which shows that they are a loose collection of unrelated fungi rather
than a true taxonomic group, and can lead to reclassification into one of the other classes. This can lead to
taxonomic duplication, with the organism allotted a new name based on the reproductive form (which should
take priority) while still retaining its old name.
The Ascomycetes and the Deuteromycetes are the most represented in the marine environment and been the
most investigated chemically.
The great majority of fungal secondary metabolites have been isolated from fungi associated with other
organisms. Examples of natural products isolated from non-associated marine fungi include the simple
polyketide Phomoxin, the carotenoid Neurosporaxanthin and some indolopeptides from surface waters or marine
sediments.
Marine algae (green, red and brown), like higher plants, harbour a wide variety of endophytic fungal species;
for example, 116 different fungal strains were cultivated from a single specimen of Fucus serratus. It is not in
general known whether any particular relationship should be considered as symbiotic, benign or pathogenic.
There are usually strong structural similarities between the natural products from these epiphytic marine fungi
and their terrestrial equivalents.
Fungal mycelia are also found in marine animal tissues. Evidence for their presence is based entirely on
culturing experiments and as yet there is no evidence from direct microscopic examination or other techniques.
cix
Their role is unknown. In general, compounds produced by fungi associated with marine animals are structurally
related to other fungal metabolites and are distinct from natural products produced by the animal organisms
themselves. It does not appear that fungi are the biogenetic source of natural products isolated from marine
invertebrates, unlike the situation found with bacteria. An example of a natural product isolated from a spongeassociated
fungus is Ulocladol, while Epicoccamide is an example of a substance isolated from a fungus associated
with a cnidarian (a jellyfish). Other series of characteristic fungal products have been isolated from fungi
associated with all other classes of marine invertebrates, as well as from fungi parasitic on fish.
The most characteristic sterols of all fungi are Ergosterol and related ergostanes. Reports of 5,7-dienic steroids
from other marine species are suggestive of fungal contamination. Other steroids isolated include Fusidic acid,
and the Gymnasterones from an ascomycete-sponge association.
There are very few reports of the incorporation of halogens. Most fungal secondary metabolites are based on a
polyketide biogenesis, but some terpenoids are found, for example the unusual nitrobenzoyl esters of 6,7,14-
Trihydroxy-8-drimen-12,11-olide and the Hirsutanols from a sponge-associated fungus. The alkaloids obtained
from marine fungi are dominated by diketopiperazines/indoles, as is the case with terrestrial fungi.
Very few biosynthetic studies have been reported for natural products specifically from marine fungi.
Dictionary of the Fungi , 9th edn, (eds. Kirk, P.M. et al ), CABI publishing, 2001
Bugni, T.S. et al, Nat Prod. Rep., 2004, 21, 143 163 (rev)
Moore, B.S., Nat. Prod. Rep., 2005, 22, 580 593 (rev)
Ebel, R., Frontiers in Marine Biotechnology, (eds. Proksch, P. et al ), Horizon Bioscience, 2006, 73 143 (secondary
metabolites from marine fungi)
3.7 PORIFERA (sponges) (ZS)
The sponges are considered as the most primitive of the multicellular organisms, providing an evolutionary
bridge between the monocellular eukaryotes and the rest of the animal kingdom. They are multicellular
organisms lacking all organ differentiation (including gonads) and some can uniquely reconstitute themselves
after passing through a sieve. They are almost exclusively marine. Sponges are found at all marine depths but the
proportion of calcareous sponges diminishes with depth owing to the physicochemical effect of pressure on the
ability of the organisms to secrete calcium.
The taxonomy of sponges is particularly difficult owing to the paucity of well-marked morphological feature
by which they can be distinguished. Many species have been synonymised and genera renamed (e.g. Aplysina =
Verongia), and there are numerous views on their classification at higher levels; a recent multi-volume treatise
(Hooper et al , 2002) proposes many changes. Three main subdivisions have been generally recognised, depending
on the nature of the skeletons that they secrete; calcareous (ZS1000), siliceous or askeletal. The largest group is
the demosponges, about 95% of known species, in which the skeleton is of spongine, a proteinaceous polymer
similar to keratin. The Hexactinellida sponges, characterised by silica spicules of 6-fold symmetry, are found only
at great depth and have been little studied chemically.
In this database a simple classification into four groups is used, which is based on Hooper (2002) as
summarised in tabular form by Kornprobst (2005). This divides sponges into; Calcareous sponges (ZS1000),
Homoscleromorphous demosponges (e.g. Plakortis ) (ZS3000), Tetractinomorphous demosponges (e.g. Stelletta )
(ZS4000) and Ceractinomorphous demosponges, (e.g. Agelas ) (ZS5000).
Sponges participate in a wide range of symbiotic/commensal relationships, and a large number of the
isolations of natural products earlier reported from them are in fact owing to the presence of cyanophytes in
particular. It is estimated that the biomass represented globally by sponge-cyanophyte symbionts is greater than
that of the sponges themselves. Given the extent of these associations, it is not surprising that the diversity of
natural products reported from sponges and sponge aggregates covers the whole range of known types. Other
natural products reported may be true metabolites of the symbionts.
A wide variety of cell membrane components have been isolated, not only extensive series of both straightchain,
branched and methylenic (cyclopropanoid) fatty acids but alkylglycerols (e.g. Raspailynes) and hopanoids
based on Bacteriohopanetetrol and relatives as well as a vast range of steroids. There are also numerous
brominated and a-hydroxyacids. Certain linear terpenoids such as the Furospongins have also been postulated to
play a role in membrane structure. Associated with the membrane structure is a wide variety of glycolipids, many
of them of unique structural type. The simpler N-containing parents are the Sphingosines, the Dictionary entries
for which include their N-acyl derivatives collectively known as ceramides, and their glycosides, known as
cx
glycosphingolipids or cerebrosides. More complex types of sphingosine such as the Plakosides (containing
cyclopropa fatty acids) have individual entries. The nitrogen-free glycolipid content also includes some structural
types not found elsewhere, such as the Crasserides (ether glycerides of a 5-membered cyclitol), which as a class
have been suggested to be uniquely diagnostic of the Porifera and found in all species examined. A unique class of
compounds so far discovered only in sponges is the range of carotenoids aromatised in one or both rings such as
Renieratene and Tethyanin.
Among calcareous sponges the most investigated genera are Clathrina and Leucetta . These genera have
yielded in particular long-chain unsaturated aminoalcohols such as the Leucettamols, a range of imidazole (e.g.
the Naamines) and other alkaloids, and cyclic peptides, (e.g. Leucamide A).
By far the most studied have been the demosponges, reflecting their numerical preponderance and shallowwater
accessibility. Demosponges contain a very wide range of steroids, which encompasses not only the
conservatively modified structures biogenetically not far removed from cholesterol (ergostanes, stigmastanes)
found in the algae, but also a large number showing more profound modification. These include 19-norsteroids
such as Hapaioside and a range of A-ring abeosteroids (3-hydroxymethyl-A-norsteroids). The most common type
of modification, however, is further side-chain methylation which leads to an extensive series of steroids having
various branching patterns up to C32, (e.g.; C29, Aplysterol; C30, Stelliferasterol; C31 Axinyssasterol; C32 (26,27-
Dimethyl-26-methylenestigmast-7-en-3-ol). Side-chain cyclopropasterols such as Calysterol and Aragusterol A
occur in the range C27-C31 and there are also many secosterols with fission at 5,6- (e.g. Hipposterol), 8,9-
(Jereisterol A), 8,14- (Jereisterol B) and 9,11- (Blancasterol). There are also many polyhydroxylated and sulfated
sterols of the type found also in many other marine organisms, and many steroidal glycosides. Halogenated
steroids (e.g. Aragusterol C) and steroidal alkaloids (e.g. Plakinamines) are rare.
Demosponges of the genera Plakortis and Plakinastrella (order Homosclerophorida) contain a wide range of
oxylipins, including many cyclic peroxides such as the Plakortides.
Another group of unusual natural products found in sponges are the terpenic isocyanides R-NC such as 7,20-
Diisocyanoisocycloamphilectane, together with their related isothiocyanates R-NCS, isocyanates R-NCO and
formamides R-NHCHO. In the appropriate DMNP entries these are grouped as derivatives under the parent
isocyanide, reflecting the fact that they have a common biogenetic origin, the isothiocyanates and formamides
apparently being derived in vivo from the isocyanides (and not the other way round as was formerly proposed).
However the biogenetic origin of the isocyanides themselves has not yet been completely solved.
A wide range of alkaloids and terpenoids are found in demosponges. Indole alkaloids range from simple
halogenated indoles such as the Plakohypaphorines to polycyclics such as the pentacyclic pyridoacridines (e.g.
Meridine). Demosponges are the most prolific of all marine organisms in terms of the secondary metabolites that
have been isolated from (but not necessarily produced by) them. In order to get a good overview, the best route is
to search the CD-ROM version of the Dictionary using the search term ZS* (all sponges), but further
information can also be obtained from the introductory sections dealing with terpenoid and alkaloid types, and of
course by perusing the pages of the printed Dictionary.
Faulkner, D.J. et al, Pure Appl. Chem., 1994, 66, 1983 1990 (rev)
Fattorusso, E. et al , Progress in the Chemistry of Organic Natural Products, (eds. Herz, W. et al ), SprigerWien,
New York, 1997, Vol. 72, 215 301 (rev, sponge glycolipids )
Watanabe, Y. et al, Sponge Sciences: Multidisciplinary Perspectives, Springer, Tokyo, 1997 (book)
Kuniyoshi, M. et al, Recent Advances in Marine Biotechnology, (eds. Fingerman, N. et al ), Science Publishers,
USA, 2001, Vol. 6, 29 84 (rev )
Systema Porifera: A Guide to the Classification of Sponges, (eds. Hooper, J.N.A. et al ), Kluwer/Plenum, NewYork,
2002 (book)
Moore, B.S., Nat. Prod. Rep., 2005, 22, 580 593; 2006, 23, 615 629 (rev, biosynth )
3.8 CNIDARIA (medusae, sea anemones, hydroids and corals) (ZT)
This class of organisms represents the first major development in body-plan over the undifferentiated sponges,
showing cellular differentiation into cells with different functions, but in general no well-defined organs. The
term Cnidarian replaces the older ‘Coelenterate’. This is a class of organisms typified by a carnivorous lifestyle,
the presence of specialised stinging cells (cnidocysts) used in the capture of prey and defensively, and a digestive
system consisting of a sac with only one opening. They have a basically radial body plan, which may be modified
either in the direction of a fixed polyp with a central gastric cavity (hydras), or a free-swimming medusa form
(jellyfish) in which the gastric cavity is underneath. Reproduction is sexual, producing a free-swimming larval
cxi
planula which develops into a free-swimming followed by a polyp form, although in some species only one of
these is formed.
About 10,000 species are documented, classified into two subphyla. The first subphylum (Anthozoa)
comprises the sea-anemones, gorgonians, crinoids and corals which have no free-floating phase, and a skeletal
structure consisting either of secreted calcareous minerals, or of proteinaceous material (gorgonine, analogous to
the spongine found in the sponges). The anthozoa are divided into two groups depending on their symmetry;
eightfold in the octocorals, (alcyonians or soft corals and gorgonians) (ZT1000) or sixfold or a multiple of sixfold
(hexacorals, including the sea anemones and hard corals) (ZT2000). The former subphylum is the most studied
group of the cnidarians chemically.
In general, relatively few nitrogenous secondary metabolites have been isolated. The proportion of
halogenated metabolites is also relatively low, except for halogenated briaranes from Briareum spp., such as the
Briareins. Some sea anemones owe their colour to carotenoids including Peridinin and Actinoerythrin. The former
in particular is produced by dinoflagellates, and these carotenoids work their way up the food chain to molluscs.
Octocorals are rich in prostanoids, steroids, terpenoids (but only sesqui- and diterpenes) and aromatics. The
prostanoids include a number identical with those found in higher organisms of the Prostaglandin series (A, B, E
and F), but also halogenated prostanoids containing Cl, Br and I such as the Chlorovulones, especially from
Clavularia . Further oxylipins are now being found in other cnidarians and it appears that their presence may be
ubiquitous. Series of furanoid compounds similar to Ancepsenolide elsewhere in the phylum support this
hypothesis. The hexacorals contain a range of polyunsaturated long-chain acids such as Leiopathic acid and the
Montiporynes.
Like the sponges, cnidarians contain a wide range of sterols, both typical cholesterol-related, and those with
modified side-chains. An important class is the side-chain cyclopropanoid steroids based around Gorgosterol,
although it has been shown that these are in fact produced by symbiotic dinoflagellates. Yonarasterol I is an
example of this group showing halogenation at C-6. There are many polyhydroxylated steroids, often showing
side-chain epoxidation, for example the Hippuristerols, and a considerable number of secosteroids, some of
unusual type such as Nicobarsterol. Also are encountered pregnane glycosides (Verrucoside, Pregnediosides and
others). In contrast to the sponges, however, O-sulfation is absent. The hexacorals produce polyhydroxylated
ecdysteroids such as Zoanthusterone which are thought to protect the organism against crustacean larvae.
The sesqui- and diterpenes found in the octocorals are diverse and include some skeletons unique to them
(nardosinanes, capnellanes, sterpuranes and some others), which in most cases are unique to certain families. In
contrast, terpenoids are almost absent from the hexacorals. The sesquiterpene hydrocarbon content of octocoral
tissues may be exceptionally high and they are thought to play an ecological role as predator and larval
implantation repellents. An important feature is the frequent occurrence of common terpenoids of the
enantiomeric series to that familiar from terrestrial plants, as shown for example by g-Maaliene and a-Copaene.
There is a complete absence of the isocyanides characteristic of the sponges, and only a limited range of terpenoid
alkaloids such as Clavulinin. The well-known skeletons represented include many furanoterpenes. The hexacorals
have yielded only a few sesquiterpenes; some lepidozanes and secolepidozanes, e.g. Anthoplalone.
The octocorals are very rich in diterpenoids, with over 1500 belonging to 50 skeletal types isolated. As with the
sesquiterpenes, some skeletons are widespread throughout the phylum, while others are restricted to a single
family and can be considered as chemotaxonomic markers. Particularly widespread skeletons include cembrane
(including norcembranes and some dimers such as Sinuflexlin), xenicanes, lobanes, briaranes, cladiellanes,
dolabellanes and amphilectanes. As with the sponges, many skeletons are prenylogues of widespread
sesquiterpenoid skeletons. The briaranes are particularly numerous and unlike most other skeletons, frequently
halogenated (chlorine only).
Some diterpene alkaloids have been found such as the Sarcodictyins (imidazoles containing the eunicellane
skeleton, closely related to briarane). The hexacorals produce a range of ceramides, often containing unusual
sphingosines, and some other acyclic amides such as Sinulamide. Their range of cyclic alkaloids is restricted, e.g.
the Villagorgins, Calliactine, but includes the unique class of fluorescent pigments based on the cycloheptadiimidazole
skeletons of Parazoanthoxanthin A and Pseudozoanthoxanthin A.
Hexacorals of the order Zoantharia (genus Zoanthus) have yielded a range of polyketide alkaloids similar to
Zooxanthellamine. Chemically and pharmacologically, the most significant natural product isolated from
cnidarians is probably Palytoxin. Hexacorals inhabiting surface waters also contain a range of mycosporins such
as Mycosporin-Gly which are closely related to analogues found in fungi and appear to perform a photoprotective
function. They also contain a range of small nitrogenous betaines and other amines, some purines such as
Caissarone, and some simple indole-imidazole alkaloids centred on Aplysinopsin.
cxii
The other subphylum of cnidarians (Medusozoa) comprises the Cubozoa (box jellies, ZT5000), Hydrozoa
(hydras, ZT6000) and Scyphozoa (true jellyfish, ZT7000). Chemical studies have been mostly confined to their
venoms, which are peptides. (See for example the entry for Anemonia sulcataToxin). One difficulty associated
with studying their secondary metabolites is the large amount of water in the tissues, which can reach 98%.
Some steroids have been identified, plus a small range of polyketides e.g. Solandelactones, Lytophilipines, and
some anthracenoids, e.g. Garvins, and simple alkaloids, e.g. Corydendramines, Tridentatols. There are also the
nitrogenous compounds associated with the bioluminescence of some species; Cypridina Luciferin and
Coelenterazine.
Faith, F.M.Y. et al, Recent Advances in Marine Biotechnology, (eds. Fingerman, N. et al ), Science Publishers,
USA, 2001, Vol. 6, 85 100; Venkateswarlu, Y., ibid , 101 143 (revs, coral )
Anderluh, G. et al , Toxicon, 2002, 40, 111 124 (rev, anemone toxins)
3.9 PLATYHELMINTHES (flukes, tapeworms and free-living flatworms) (ZU1000)
These are the flatworms, characterised by a bilateral body plan and the complete absence of a digestive cavity.
About 18,000 species are known. They may be terrestrial, freshwater or marine and many belong to orders which
are exclusively parasitic (e.g. flukes). The majority of marine species belong to the class of planarians
(turbellarians). These are mobile, carnivorous animals having no physical means of defence and relying entirely
on substances absorbed or modified from the diet, or produced by symbiotic organisms, as chemical antifeedants.
The most studied genus is Amphiscolops. These worms are protected by Amphidinolides produced by symbiotic
dinoflagellates and contain other dinoflagellate products such as Luteophanols. Other planarians feeding on
ascidians have yielded alkaloids (e.g. Lepadins, Villatamines).
3.10 ANNELIDA (trueworms) (ZU3000)
These are the segmented worms, having an alimentary canal. They include the polychaetes, oligochaetes
(earthworms; mostly terrestrial), hirudineans (leeches; mostly freshwater), echiurians and Vestimentifera. They
locomote by means of bristles which can be irritant or venomous. The best-known genus among the echiurians is
the spoonworm Bonellia viridis, most studied on account of its tetrapyrrole pigment Bonellin which also plays a
role in inducing sexual differentiation in the larva. The Vestimentifera include the recently-discovered giant
hydrothermal vent dwellers Riftia which coexist with sulfur bacteria, and store elemental sulfur in the tissues.
There has so far been little study of lipid or steroid content. Their carotenoid pigments appear to be
mainstream components such as Astaxanthin, derived dietetically. Other annelid pigments are anthracenes and
anthraquinones, such as Hallachrome. Annelids also contain brominated phenols (e.g. 2,6-Dibromophenol) and
derived aromatics such as Thelepin, which protect them against bacteria.
Certain annelids bioluminesce and in Odontosyllis spp. this is based on pteridines such as 6-Propionyllumazine.
Nereistoxin is a simple aminodithiolane with powerful cytotoxic properties produced by Lumbriconereis sp. Some
annelids contain large amounts of Hypotaurine and Thiotaurine.
3.11 OTHER VERMIFORM GROUPS (ZU5000)
The ribbon-worms or nemerteans have yielded the powerful nicotinic receptor agonist Anabaseine, used as a
venom by the worm, together with several related oligopyridines. Toxins of the tetrodotoxin series are also found
in the tissues, and also some peptide toxins, which have only been investigated fully for one species, Cerebratulus
lacteus (see Neurotoxin B-IV)
The unsegmented phoronidian worms Phoronopsis have yielded antibacterial bromophenols like those
obtained from the annelids.
3.12 BRYOZOA (ZU6000)
These colonial organisms are entirely aquatic and mostly marine. They are distinguished by their unique form of
gastric cavity, which is surrounded by tentacles forming an organ called the lophophore. The colonies are
produced by budding and therefore consist of genetically identical individuals, each of which is surrounded by a
bilayered exoskeleton, the inner layer calcareous (not always continuous) and the outer layer chitinous. They are
suspension feeders, feeding on plankton and bacteria, and are found at all depths.
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Bryozoans have so far been less studied than the number of known species (5700) would justify given the range
of interesting natural products already isolated from them. This is probably a consequence of the difficulty of
harvesting them.
Terpenoids and steroids have been little studied. A number of common mono-, di- and triterpenes (e.g.
Cuminol, Neoabietic acid, Ursolic acid or a stereoisomer) were reported from Conopeum sp., but this work needs
confirmation. The single diterpenoid Murrayanolide that has been obtained apart from this work has a unique
skeleton which implies that many more unusual terpenoids may exist on other bryozoans. The similarly limited
studies of steroid content have yielded only relatively common types based on cholestane methylated in the side
chain and/or hydroxylated. One or two anthraquinone pigments have been characterised, of which the most
unusual is Bryoanthrathiophene.
The most numerous metabolites from bryozoans are defence chemicals, which comprise numerous alkaloids,
and the Bryostatins, an important series of polyether polyketide toxins with anticancer properties, some of which
have also been found in other marine organisms. The ultimate source of these may be Candidatus bacteria.
The range of alkaloids is extensive taking into account the limited amount of work that has so far been done.
There are simple halogenated phenethylamines (Convolutamines, Volutamides). Pyrroles and pyrrolidines include
Tambjamines (originally isolated from animals higher up the food chain, and which could be tetrapyrrole
degradation products), Amathamides, Amathaspiramides and Convolutamides. Indoles are mostly brominated
simple indoles (Flusrabromine, Alternatamides) but Flustra foliacea yielded a series of Flustramines and related
alkaloids of the physostigmine type (VX4100) unique in the marine environment. The Securamines, Chartellines
and Chartellamides represent a further elaboration of this structural type up to a maximum of seven rings. There
are also a number of quinolinequinones, halogenated or bearing thioether substituents (Perfragilins,
Caulibugulones). The presence of nitro groups in a few alkaloids including the purinoid Phidolopin is notable.
Kerr, R.G. et al, Recent Advances in Marine Biotechnology, (eds. Fingerman, N. et al ), Science Publishers, USA,
2001, Vol. 6, 149 164; Prinsep, M.R., ibid , 165 186; Kem, W.R., ibid , 187 (revs )
3.13 MOLLUSCA (ZV)
This is a diverse and widely distributed phylum of organisms. The body plan is basically nonsegmented and
bilateral, although in some molluscs (the gastropods) it is often modified by torsion into a spiral surrounded by a
shell. There are well- developed organs inside a more or less thickened outer layer, the mantle, which secretes a
shell formed of calcareous matter and protein. This shell may be external, as in the gastropods, internal as in
squids, or may be totally lacking (octopuses and nudibranchs). There is generally a muscular foot and a cephalic
region which may be highly developed into tentacles and other organs, as in the cephalopods. The alimentary
canal is well developed and furnished with a rasping radula used in feeding. Different classes of molluscs show
variation in this general body plan, for example the bivalves have a hinged shell, no cephalic region and no
radula, and some of them also lack the foot. Many species of mollusc are known, present in marine, freshwater
and terrestrial environments, ranging in size from microscopic to very large. They show a wide range of dietary
behaviour (carnivores, herbivores, filter feeders and detritus feeders) and undergo a wide range of symbiotic
relationship. In particular, in some molluscs the mantle incorporates symbiotic algae providing toxic
antipredator substances.
The phylum is usually divided taxonomically into seven unequal classes, but of these four (including Chitons,
ZV1000) are numerically limited and have been studied chemically little or not at all. The most important classes
both in terms of number of species, economic importance and chemical studies are the gastropods (ZV2000,
ZV3000, ZV4000), the bivalves (ZV6000) and the cephalopods (ZV8000). However, the bivalves with their welldeveloped
physical protective mechanism of the double shell, appear to have less need for chemical defence
mechanisms and their secondary metabolites are less profuse. They have mostly been studied in terms of their
economically important shellfish toxins, which are in fact microbial/dinoflagellates products. The cephalopods
too have been rather little studied; their most characteristic metabolites are Adenochromines. The most studied
organisms chemically have been various types of gastropod which have little or no physical defence and rely
almost entirely on chemical defence against predators.
The numerous gastropods are sometimes further divided into three subclasses, the Prosobranchia (ZV2000)
the Opisthobranchia (ZV3000) and the Pulmonata (ZV4000). (This division is not recognised by the Catalogue of
Life, but since it is a convenient subdivision of a large group of natural product-producing organisms it is
followed here). A table of these subdivisions is given in Kornprobst (2005), Chapter 23, which also gives a more
detailed description of the secondary metabolites of gastropods organised by class and subclass.
cxiv
Terpenoids are numerous. The genus Planaxis (Gastropoda, Prosobranchia) has provided a series of
cembranoids such as Jeunicin and Planaxool. Among the opisthobranchs, the sea hares or aplysians, which are
herbivorous, feed on cyanobacteria and algae, and their digestive systems and mantles contain a wide variety of
unchanged and metabolised secondary metabolites which perform an antifeedant function. These alimentary
chains are complex and have been much studied. The two most studied genera are Aplysia and Dolabella; the
former feed mostly on red algae and contain many halogenated and nonhalogenated terpenoids (Kurodainol,
Aplysin 20, Brasilenol, Punctatol and many others), cyclic halogenated ethers (Dactylyne, Aplyparvunin, etc.),
lactones (e.g. Aplyolides, Aplyronines), and both peptide and nonpeptidal alkaloids (Aplaminone). Dolabella spp.
feed on brown algae, and in accordance with the terpenoid profile shown by these, contain mostly
nonhalogenated diterpenoids (Auriculol, Dolatriol) as well as lactones (Dolabelides), peptides (notably the
extensive range of highly cytotoxic Dolastatins, from cyanobacterial symbiosis) and alkaloids. A few Aplysia spp.
feed on brown algae and also contain nonhalogenated diterpenes, e.g. 4-Hydroxycrenulide. Other products
isolated from this type of mollusc appear to derive from symbiotic/commensal green algae (Aplyolides) and even
fungi (Aplysiatoxin).
The shell-less nudibranchs can incorporate cnidocysts obtained from cnidarians into their mantle, and also
rely heavily on compounds, especially terpenes, ingested in the diet as a means of defence. A wide range of
skeletal types have been isolated, and include sponge-derived terpenoid isocyanides and compounds derived
metabolically from them, such as the Acanthenes, and sponge-derived scalarane sesterterpenoids such as
Deoxoscalarin. However, nudibranchs also synthesise terpenoids de novo via the mevalonate pathway. Many
terpenoids are present as glyceryl esters such as the Anisodorins and the Verrucosins. In general it is possible to
predict with a fair degree of accuracy what types of compound (though not necessarily the exact compounds) that
will be isolable from nudibranch tissues by studying the prey of the different species. The sacoglossan gastropods
also contain a range of terpenoids, but these animals are herbivorous and the terpenoids derive from commensal
green algae entering into the tissues (e.g. Ascobullins). A number of degraded chlorophylls such as Chlorophyllone
a have been isolated from bivalve molluscs, which have also yielded modified carotenoids (Pectenoxanthin,
Crassostreaxanthins)
Nudibranchs contain a narrow range of carotenoids (e.g. Hopkinsiaxanthin) and steroids (Lovenone, a
secosteroid, for example). Other defence allomones include quinonoid and related meroterpenoids, and
macrocyclic lactones (Laulimalide, Sphinxolides, the isoxazolide lactone Kabiramides and others, some of these at
least probably cyanobacterially derived). Also noteworthy is the isolation of prostanoid lactones from Tethys
fimbria .
The distribution of polyketides in molluscs is patchy. They are found only in some classes of the gastropods,
for example the Auripyrones (strictly, polypropionates) from Dolabella, the Aglajnes from Bulla spp. which are
preyed upon by carnivorous molluscs Aglaja , and Tridachiapyrones from the herbivourous sacoglossans.
Pulmonarians have afforded a number such as Muamvatin, Maurapyrone C and the Onchitriols.
Long chain aromatic and heteroaromatic metabolites, which do not appear to be derived from the diet, are
found in Navanax spp. (Navenones, which play a role as alarm pheromones), Haminoea spp. (Haminols) and other
genera.
Peptides, especially cyclic oligopeptides often containing unusual amino acid residues, are probably widely
distributed and show structural resemblances to similar compounds found further down the food chain, e.g. in
sponges. See for example the Kulolides from Philinopsis spp. Peptides such as the Kahalalides have also been
isolated from sacoglossans, and Onchidin is an example of a cyclic oligopeptide isolated from a pulmonarian.
Nudibranchs also contain some characteristic nucleosides such as Doridosine.
Among other nitrogenous metabolites, the best-known from gastropods is the dyestuff 6,6’-Dibromoindigotin,
known since ancient times. The genus Lamellaria (Gastropoda; Prosobranchia) yielded a wide range of the
pyrrole alkaloids. The Lamellarins, which, however, are also found in ascidians on which the molluscs feed and in
sponges, are probably biosynthesised symbiotically. Other gastropods (nudibranchs) prey on bryozoans, and yield
the Tambjamines, which are also pyrroles. There are also guanidine alkaloids, e.g. Triophamine.
Similarly, the Kuanoniamines from Chelynotus (Gastropoda; Mesogastropoda) are closely similar to, though
not identical with, Dercitine and similar alkaloids isolated from sponges. Other compounds isolated bearing a
close structural relationship to sponge products include Jorumycin, which closely resembles the Renieramycins
from sponges.
Carnivorous gastropods of the genus Conus produce a vast series (there appear to be tens of thousands of
chemically distinct compounds) of highly toxic peptides the Conotoxins, which are delivered to the prey by means
of a highly specialised injecting organ. Other toxic molluscs lack this specialised delivery system and administer
cxv
toxins through the radula. Such toxins are complex alkaloids related to Tetrodotoxin and Surugatoxin and are
bacterial products (see also under fish, below).
The bivalve toxins (Yessotoxins, Pectenotoxins, Pinnatoxins, Azaspiracids, Saxitoxins) responsible for various
kinds of shellfish poisoning are mostly produced by commensal dinoflagellates and have been mentioned above.
There are differences in the distribution of different members of the saxitoxin series between the tissues of the
bivalves and the originating dinoflagellates.
The kidneys of the giant clam Tridacna maxima concentrate up to 0.1% of arsenic, the function of which is
unknown. It is stored as various dimethylarsinoylribosides.
Cimino, G. et al, Curr. Org. Chem., 1999, 3, 327 372 (rev, opisthobranchs)
Molluscs: From Chemico-ecological Study to Biotechnological Application; Progress in Molecular and Submolecular
Biology, (eds. Cimino, G. et al ), Springer, 2006, Vol. 43 (book)
3.14 ECHINODERMATA (ZW)
These organisms are characterised by a radially symmetrical body plan, (which is acquired in the adult stage, the
larvae being bilaterally symmetrical) and a unique system of respiration through water-filled tube feet which also
provide locomotion. There is a calcareous endoskeleton. This is the largest phylum of exclusively marine animals,
with about 7000 species known. They may be herbivores, suspensivores, detritivores, carnivores or necrophages,
and the carnivorous species may prey for example on corals or other echinoderms. There are many examples of
commensalism and parasitism between echinoderms and other organisms.
Although various classification schemes for echinoderms differ in detail, five main groups are generally
recognised. The taxonomy used in this Dictionary follows the Catalogue of Life scheme. The most primitive,
widely represented in the fossil record, are the Crinoids (ZW1000) in which the mouth and anus are on the same
surface. They have a planktonic larval form followed by an adult form which may be sessile (sea lilies) or mobile
(feather stars). The other four groups, in which the mouth and anus are on opposing faces, are the starfish
(Asteriodea) (ZW2000), sea urchins (Echinoidea) (ZW3000), sea cucumbers (Holothuroidea) (ZW4000) and
brittle stars (Ophiurioidea) (ZW5000).
The presence of steroidal saponins of different types in the starfish and in the sea urchins is unique in the
animal kingdom, and serves to delineate them from the other echinoderms and from each other. Other
characteristic markers are the dominance of 3a-hydroxylated steroids in the ophiurians, and of quinonoid
pigments of different types in the crinoids and in the sea urchins.
The various types of echinoderm produce a variety of specialised polysaccharides, the study of which is still in
its infancy. One which has been characterised is Frondecaside. The lipid content of sea urchins and ophiurians is
high in polyunsaturates. The starfish have been relatively little investigated but appear to follow the same pattern,
with some prostanoid precursors. A high proportion of branched-chain acids have been isolated from sea
cucumbers, but these are probably of bacterial origin. Phospholipids and glycosphingolipids appear to be
universally present in echinoderms and a wide range of structural types of ceramides and cerebrosides have been
isolated from starfish (see Acanthacerebrosides, Astrocerebrosides and similar compounds) and holothuroids.
About 30 different carotenoids have been characterised from sea urchins, mostly from the gonads, including the
apocarotenoid Paracentrone, and others from ophiuroids (Ophioxanthin). The starfish are pigmented by
carotenoids derived from the food chain and often modified by the introduction of oxo functions to give pigments
of bluer colour, such as Adonixanthin.
Throughout the echinoderms, halogenation is rare and found only in a few anthraquinone pigments such as
the Gymnochromes (from crinoids). There are also few alkaloids of greater complexity than a range of aliphatic
amines. The few exceptions to this generalisation are very probably derived from organisms such as dinoflagellates
present in the food chain. Asterina 330 is a mycosporin analogue related to such compounds found in cnidarians.
The identification of some unusual sulfur compounds is also noteworthy, for example the Hedathiosulfonic acids.
As noted above, the type and extent of steroid content is a major distinguishing feature of different types of
echinoderm. The crinoids and echinoids have been little studied, but appear to contain exclusively ‘classical’
steroid types closely related structurally to cholesterol. The ophiurians, which in some respects are intermediate
between the primitive crinoids and the more highly evolved echinoderms, contain many 3a-hydroxysteroids with
only one or two glycosides. In the starfish, the range of glycosides and of steroid sulfates is extensive, derived
from a wide range of side-chain modified parent steroids, which, however, are mostly 3b-hydroxylated. The side
chain may be degraded (e.g. Asterosterol, Hermaphrodiol) or cyclopropanated (Acanthasterol). Polyhydroxylation/
cxvi
O-sulfation of the steroid nucleus, which is widespread in marine organisms, is at its most extensive here. The
glycosides, such as the Asterosaponins play a role in chemical defence through their surface-active properties. Both
pentose and hexose residues are found.
The holothurians contain many steroids, some biosynthesised de novo from acetate via lanostane triterpenes,
others apparently derived from the diet. In Holothuria, it has been shown that two biosynthetic routes operate,
one via Lanosterol and the other via Parkeol. These biosynthetic routes provide steroids with all combinations of
presence or absence of the methyl groups at C-4 and C-14, as well as side chain variations (cholestane, ergostane
and further additional carbons). The chief distinguishing feature of the holothurians, however, is the exclusive
occurrence of specialised triterpenoid glycosides of the holostane type, the prototype for which is
Holothurinogenin but with well over 100 currently known. These appear to be derived biogenetically via Parkeol.
A smaller group showing (190/16) lactonisation is based on Posietogenin.
Examples of the anthraquinonoid pigments that are readily extracted from crinoids include Ptilometric acid.
Some of these are O-sulfates, e.g. Comantherin sulfate. The sea urchin pigments however are exclusively
naphthoquinonoid, e.g. the Spinochromes. The number of alkaloid-like compounds isolated from echinoderms is
extremely limited, e.g. Asterina 330 (a palytoxin analogue).
Stonik, V.A. et al, J. Nat. Toxins, 1999, 8, 235-238 (rev, holothuroid toxins )
Moore, B.S., Nat. Prod. Rep., 2006, 23, 615-629
3.15 CRUSTACEA (ZX8000)
The crustaceans, including the decapods, are the only type of animals in the vast arthropod phylum (ZX) that
occur to any extent in the sea. (There is also the horseshoe crab Limulus, an ancient animal related to the
arachnids, and which has a few mentions in this Dictionary, and a few saline-tolerant millipedes living in shore
environments). In the past the crustaceans have been considered a separate phylum, but they are now often
considered a major subphylum of the arthropods having in common the hard chitinous exoskeleton and the body
divided into head, thorax and abdomen. About 60,000 species are known, some of them (ostracods, e.g.
Cypridina , and copepods, e.g. Calanus) very small planktonic organisms. The best-known large species are the
decapods (crabs and lobsters). Chitin, derived industrially from crab shells, is an important industrial material.
Chemical studies on crustaceans have been fragmentary and are mostly confined to their carotenoid pigments,
some of which have also been obtained from other marine organisms but which were originally characterised as
crustacean products. These are mostly derived by a variety of oxygenations of the terminal rings of the
carotenes, and include Astaxanthin, Crustaxanthin, Zeaxanthin and various others.
The moulting hormones of crustaceans are terpenoid (Methylfarnesate) and steroidal (Ecdysone/Crustecdysone),
the latter being common to insects also. Steroid studies have been fragmentary and have indicated a
preponderance of cholesterol and closely related compounds. Various endohormones such as testosterone, similar
to their mammalian equivalents, have been shown to be present in crustaceans but these are mostly not included
in the Dictionary.
The simple pyridine Homarine and the arsenical Arsenobetaine are widespread in nature but were first isolated
from crustaceans.
3.16 HEMICHORDATA (ZY1000)
This is a numerically limited class of animal (about 100 species recorded), consisting of two surviving types of
organism; the acorn worms (Enteropneusts) inhabiting temperate and tropical waters, and the pterobranchs,
colonial animals inhabiting chitinous tube galleries and found in polar waters. There is differentiation of the body
into three well-defined zones, and they have some but not all of the morphological characters that define the
chordates. Two types of natural product have been identified from them. The first is a range of toxic
cyclohexanes (e.g. Bromoxone), halogenated phenols (e.g. 2,4-Dibromophenol) and halogenated indoles
(Glossobalol) isolated from Ptychodera, Balanoglossus and Glossobalanus spp. respectively. These are used by
the worms as defence chemicals, and are of environmental significance. Of greater biochemical interest are the
highly cytotoxic disteroidal metabolites the Cephalostatins from Cephalodiscus gilchristi. Owing to the difficulty
of culturing hemichordate species, there is no information currently available concerning their possible
distribution elsewhere in the phylum, or on their biosynthesis.
cxvii
3.17 PROTOCHORDATA (ZY5000)
These simplest chordate animals are generally divided into two unequal groups; the urochordates (tunicates) and
the cephalochordates which are free-swimming bilaterally symmetrical animals (Amphioxus). Protochordates are
the most developed of the invertebrates and have a notochord which is the evolutionary precursor of the spinal
column characteristic of the vertebrates. They are exclusively marine. The larger group of urochordates is divided
into three classes. Of these, two, including the free-floating salps, have been little investigated.
Most chemical studies have been on the third group, the sessile ascidians or sea squirts. These are filter feeders,
often harbouring commensal cyanobacteria and other organisms which may be the true source of some of the
reported natural products. Their chemistry is dominated by the presence of an extraordinary range of mostly
biologically potent nitrogen compounds. The ascidians also famously accumulate vanadium to a very high concentration
in specialised cells, and some have highly acidic tissues (down to pH 1). Other metals are also accumulated,
as shown by the presence of Tunichlorin, probably the product of metabolism of a commensal organism.
The epidermis of ascidians contains a range of sulfated glycans, including some unusual residues such as LIduronic
acid, and the unusual polysulfated polymannose Kakelokelose. The membrane lipids have been little
studied, and presumably are close to those of other higher organisms in structure. A few oxylipins have been
isolated, such as Didemnilactone and Lissoclinolide. Ceramides and cerebrosides appear to be widespread as in the
echinoderms, with some unusual types such as Didemniserinolipids isolated. Ascidians contain a range of
carotenoids, both common ones and some rarer ones such as Halocynthiaxanthin and Amarouciaxanthins
probably derived from metabolic alteration of commoner carotenoids present in the filtered plankton. The
steroids so far identified lack the wide structural range shown by the echinoderms and are mostly straightforward
cholestanes and ergostanes, with some 5,8-epidioxysteroids and secosteroids, e.g. Aplidiasterols. The Ritterazines
from Ritterella have disteroid structures linked by a central pyrazine ring, showing close structural similarity to
the cephalostatins from hemichordates.
Non-nitrogenous secondary metabolites are few in number. These include some small acetogenins such as the
Didemnenones. Terpenoids are rare; the Haterumaimides are unusual not only in being diterpenes but also in being
chlorinated; however, they may derive from Prochloron symbionts. Ritterella spp. provided some furanoterpenoids
related to Dendrolasin such as 8-Hydroxydendrolasin but Dendrolasin itself was not present, and the depth
of dredging would rule out a sponge symbionts, so their origin is obscure. Several series of meroterpenoids have
been isolated, especially from the Polyclinidae, such as the Verapliquinones and the structurally complex ansacompounds
the Longithorones from Aplidium.
Among the nitrogenous metabolites, many of which doubtless also spring from commensal organisms, there is
a very wide range of structure including some with, and some without, analogies in other phyla.
Firstly, there is an extensive range of modified peptides and depsipeptides. Several series of these are
macrocyclic thiazoles and oxazoles, for example the Comoramides, the Bistratamides, the Lissoclinamides and the
Patellamides. Other cyclic depsipeptides are more strictly peptide-related, although containing a range of unusual
amino acids. The most studied have been the Didemnins and their relatives.
Heterocyclic alkaloids are numerous and include the extensive range of pyrroloisoquinolines the Lamellarins
which were first isolated from molluscs but which are the products of ascidians on which they prey, or possibly of
a symbiotic association involving sponges. These, like the Ningalins, are probably derived biosynthetically from
DOPA. Quinoline alkaloids are represented by the Trididemnic acids and the basic quinoline ring system is further
elaborated into pyridoacridines, e.g. Ascididemin and other polycycles. These too are also found in other marine
organism classes. In the ascidians they fulfil the role of pigmentation, and are also mostly cytotoxic.
Indole alkaloids are also numerous, again known mostly as polycyclic condensed systems, e.g. Fascaplysin. For
a fuller count of the numerous ascidian alkaloids, it is necessary to search the main body of the Dictionary.
Ascidians also contain a wide range of sulfur compounds, both sulfur-heterocycles and polysulfides, such as the
aromatic Lissoclinotoxins.
Davidson, B.S., Chem. Rev., 1993, 93, 1771 1791 (rev)
3.18 PISCES (fish) (ZZ1000)
The fish represent the most numerous of marine vertebrates. They are well studied taxonomically and extensively
documented in the online database Fishbase (a contributor database to the Catalogue of Life). They can be
divided into cartilaginous fishes (e.g. sharks), and the larger category of bony fishes, considered to be the more
highly evolved. Their commercially important lipids have been extensively studied; see for example Squalene.
cxviii
The cartilaginous fishes contain a wide range of polyhydroxylated nitrogenous and non-nitrogenous sterols,
based on 5b-cholestane. Examples are Chimaerol and the important drug Squalamine. The colour of different fish
is due to the presence of various carotenoids and xanthophylls, including Astaxanthin, Salmoxanthin, Idoxanthin
and Tunaxanthins.
The sexual development of many species of fish is determined by the presence of steroids in the water. Many of
the studies have been on freshwater species such as the goldfish, but 17a,20b-Dihydroxypregn-4-en-3-one as its
20-sulfate is known to be a hormone of the male Atlantic salmon together with Testosterone.
The fish products that have received the most chemical attention, apart from the lipids, are the toxins
produced by various species. These may be steroidal (e.g. Pavoninins), peptide (Grammistins) or alkaloid-like,
such as the much-studied Tetrodotoxin and its relatives from fugu fish (various species of the Tetraodontidae).
The latter, however, are metabolites of Pseudomonas bacteria or dinoflagellates in the fish, and are also found in
other marine organisms and even terrestrial ones.
Some fish secrete peptide venoms in specialised spines to deter prey. An example is the powerful poison
Stonustoxin from the stonefish.
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