|Mycosporine-like amino acids and marine toxins--the common and the different.|
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|PMID: 18728764 Owner: NLM Status: MEDLINE|
|Marine microorganisms harbor a multitude of secondary metabolites. Among these are toxins of different chemical classes as well as the UV-protective mycosporine-like amino acids (MAAs). The latter form a group of water-soluble, low molecular-weight (generally < 400) compounds composed of either an aminocyclohexenone or an aminocyclohexenimine ring, carrying amino acid or amino alcohol substituents. So far there has been no report of toxicity in MAAs but nevertheless there are some features they have in common with marine toxins. Among the organisms producing MAAs are cyanobacteria, dinoflagellates and diatoms that also synthesize toxins. As in cyclic peptide toxins found in cyanobacteria, amino acids are the main building blocks of MAAs. Both, MAAs and some marine toxins are transferred to other organisms e.g. via the food chains, and chemical modifications can take place in secondary consumers. In contrast to algal toxins, the physiological role of MAAs is clearly the protection from harmful UV radiation by physical screening. However, other roles, e.g. as osmolytes and antioxidants, are also considered. In this paper the common characteristics of MAAs and marine toxins are discussed as well as the differences.|
|Manfred Klisch; Donat-P Häder|
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|Type: Journal Article; Review Date: 2008-05-22|
|Title: Marine drugs Volume: 6 ISSN: 1660-3397 ISO Abbreviation: Mar Drugs Publication Date: 2008|
|Created Date: 2008-08-27 Completed Date: 2008-12-05 Revised Date: 2009-11-18|
Medline Journal Info:
|Nlm Unique ID: 101213729 Medline TA: Mar Drugs Country: Switzerland|
|Languages: eng Pagination: 147-63 Citation Subset: IM|
|Department for Biology, Friedrich-Alexander University, Staudtstr. 5, 91058 Erlangen, Germany. firstname.lastname@example.org|
|APA/MLA Format Download EndNote Download BibTex|
Amino Acids / metabolism*
Antioxidants / metabolism*
Cyanobacteria / metabolism
Dinoflagellida / metabolism
Marine Toxins / metabolism*
|0/Amino Acids; 0/Antioxidants; 0/Marine Toxins|
Journal ID (nlm-ta): Mar Drugs
Journal ID (publisher-id): MD
Publisher: Molecular Diversity Preservation International
? 2008 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland
License:This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Received Day: 7 Month: 3 Year: 2008
Revision Received Day: 9 Month: 5 Year: 2008
Accepted Day: 13 Month: 5 Year: 2008
collection publication date: Month: 3 Year: 2008
Electronic publication date: Day: 22 Month: 5 Year: 2008
Volume: 6 Issue: 2
First Page: 147 Last Page: 163
Publisher Id: md6020147
PubMed Id: 18728764
|Mycosporine-Like Amino Acids and Marine Toxins - The Common and the Different|
|Department for Biology, Friedrich-Alexander University, Staudtstr. 5, 91058 Erlangen, Germany; E-mails:
|Correspondence: * Author to whom correspondence should be addressed.
Natural products from marine organisms have attracted increasing research interest in recent years [1,2]. The number of newly reported marine compounds increased steadily over the last decades up to almost 4000 new compounds described between 2001 and 2005 . A wide variety of products from marine algae are of high actual or potential economic impact. Polyunsaturated fatty acids, carotenoids and phycocolloids are examples for marine products used in the food industry, while other compounds serve as templates for the development of new pharmaceutical drugs .
A remarkable group of marine natural products are the mycosporine-like amino acids (MAAs). An outstanding characteristic of these compounds is their high UV absorption with molar absorptivities (?) of around 40 000 l mol?1 cm?1 (e.g. ). MAAs are water-soluble, low molecular-weight (generally <400) compounds composed of either an aminocyclohexenone or an aminocyclohexenimine ring, carrying nitrogen or amino alcohol substituents (see Fig. 1A) . They are found in a wide variety of marine, freshwater and to a smaller degree in terrestrial organisms . There is limited evidence that MAAs are derived from early steps of the shikimate pathway [7,8]. However, the biochemical pathway of MAA synthesis is still largely unknown, as well as its genetic base. The most primitive organisms capable of MAA synthesis are cyanobacteria (apart from one single bacterial species ). Among eukaryotic life, MAAs are synthesized in algae, fungi and lichens (symbioses between algae or cyanobacteria and fungi). Animals, which are lacking the shikimate pathway, but nevertheless contain MAAs in their body, are believed to derive these compounds either from their food or from symbiotic algae or cyanobacteria [10,11]. Recently this view has been challenged by the report of genes enconding enzymes of the shikimate pathway in the genome of a marine animal .
The function of MAAs in phototrophic organisms is primarily the protection of the organisms from deleterious UV radiation [13?15], but additionally they may function as compatible osmolytes  or as antioxidants . Due to their high photostability MAAs are interesting candidates as UV sunscreens in cosmetic formulations [18,19]. Other UV absorbing compounds found in nature include scytonemins [20,21] and usnic acid . The occurrence of these compounds is much more restricted than that of MAAs: Scytonemins are found only in cyanobacteria and cyanobacterial lichens [21,23] and usnic acid only in lichens . Similar to MAAs, the synthesis of scytonemins and usnic acid is triggered by UV radiation and UV protection is an important function of these compounds [22,25]. In spite of these similarities, this review will focus on a comparison between MAAs and marine toxins.
Marine toxins have a tremendous economical impact due to their deleterious effects . Poisonings by marine toxins can be grouped according to the chemical structures of the causative toxins and main symptoms of intoxication : 1: Paralytic shellfish poisoning (PSP), caused by a group of closely related tetrahydropurine compounds including saxitoxin (STX), the first chemically characterized PSP toxin (see Fig. 1 B). 2: Diarrheic shellfish poisoning (DSP), caused by heat-stable polyether and lipophilic compounds isolated from various species of shellfish and dinoflagellates. 3: Domoic acid (see Figure 1 B) causing amnesic shellfish poisoning (ASP) sometimes also referred to as domoic acid poisoning. 4: Neurologic shellfish poisoning (NSP), caused by brevetoxins, tasteless, odourless, heat and acid stable, lipid soluble, cyclic polyether neurotoxins produced by the marine dinoflagellate Karenia brevis (formerly known as Gymnodinium breve or Ptychodiscus brevis . 5: Azaspiracid shellfish poisoning, caused by azaspiracids. 6: Ciguatera fish poisoning (CFP), caused by ciguatera toxins, lipid soluble polyether compounds that are formed by biotransformation in the fish of precursor gambiertoxins. These poisonings in humans are caused by the ingestion of shellfish or fish that has accumulated toxins from their food. The primary producers of the aforementioned toxins are eukaryotic algae, mainly dinoflagellates. Only amnesic shellfish poisoning is caused by a diatom .
In freshwater environments, the main producers of toxins are prokaryotic cyanobacteria. The most frequently found cyanobacterial toxins in blooms from fresh and brackish waters are the cyclic peptide toxins of the microcystin (see Fig. 1 B) and nodularin families. Microcystins have been found in planktonic Anabaena, Microcystis, Oscillatoria (Planktothrix), Nostoc and Anabaenopsis species and in terrestrial members of the Hapalosiphon genus. Nodularin has been reported only from Nodularia spumigena . Other cyanobacterial toxins are neurotoxins, including saxitoxin and analogues, anatoxin-a(S), an organophosphorous compound that acts as a potent irreversible acetyl cholinesterase inhibitor, and anatoxin-a .
To our knowledge there are no studies published addressing toxicity of MAAs. However, it seems likely that adverse effects, if there were any, would have been found empirically due to the widespread use of MAA-containing organisms as food, such as the red macroalga Porphyra sp. , terrestrial cyanobacteria of the genus Nostoc  and shellfish , without indications of adverse effects caused by MAAs. Nevertheless, the distribution of MAA synthesis and toxin production in a number of organisms leads to the question of possible relations between these groups of bioactive compounds.
Although there are more possible functions of MAAs in an organism, the role that is assumed primarily is the protection from deleterious UV radiation. Apart from antioxidant functions that have been reported exclusively for mycosporine-glycine [34,35] possible other roles of MAAs in desiccation tolerance as well as heat and cold tolerance are far less corroborated . Merely circumstantial evidence for the UV-protective role of MAAs has been derived from the correlation of the MAA concentration and the UV radiation received by organisms. UV exclusion experiments showed that MAA concentrations in corals decline when grown under exclusion of UV radiation . Numerous studies have shown correlations of MAA concentrations with gradients of UV radiation caused by water depth (e.g. ), UV transparency of water and altitude of the lakes (e.g. ) or latitudinal gradients . Greater susceptibility to UV radiation was found in corals from deep water as compared to those from shallow water  and the photoinhibition of photosynthesis by UV radiation is decreased in dinoflagellates with high MAA concentrations induced by culture under high light conditions as compared to those with low MAA concentrations that were grown under low light. This protective effect was found, as could be expected, most pronounced in the wavelength range of maximal absorption by MAAs, i.e. between 310 and 360 nm . The dinoflagellate Gyrodinium dorsum is able to tolerate at least twice as high doses of UV-B radiation before its motility is inhibited when it has been induced to synthesize MAAs by moderate UV-A radiation beforehand .
The UV-protective effect of MAAs is derived from their strong UV absorption with high molar absorptivities, their high photostability and the ability to dissipate the absorbed energy as heat. The photostability of MAAs is very high. The quantum yield of photodecomposition of the MAAs porphyra-334 and shinorine are 2.4 10?4 and 3.4 10?4, respectively . In addition to the screening of cellular compounds from UV radiation, MAAs might also quench excited states of thymine by nonradiative energy transfer, and prevent the formation of photoproducts . There is, however, no evidence for the importance of this mechanism in vivo.
Osmoprotective functions of MAAs might be concluded from their high abundance in organisms from hypersaline environments . Highest MAA concentrations are generally found in organisms from marine or saline environments, but MAAs do not reach concentrations that could balance the osmolarity in the medium, so that additional compatible solutes, such as glycine-betaine or others, are required . The possible involvement of MAAs in osmotic regulation was demonstrated in experiments in which the salinity of the medium was reduced by dilution with fresh water: the MAAs were rapidly excreted to the medium in amounts proportional to the degree of dilution .
An additional function of mycosporine-glycine may lie in the protection from oxidative stress. Whereas imino-MAAs having an cyclohexenimine core, like shinorine and porphyra-334, are not prone to oxidation, the oxo-MAA mycosporine-glycine that is constituted by an cyclohexenone core ring (see Fig. 1 A), shows a moderate antioxidant activity  and is an effective quencher of singlet oxygen generated by photosensitization . The antioxidant activity has not only been demonstrated in vitro, but also in vivo: the coral Stylophora pistillata, containing only small amounts of mycosporine-glycine was found significantly more prone to heat-induced oxidative stress than Platygyra ryukyuensis containing a 20-fold higher concentration of mycosporine-glycine. Concomitant with the exposure to oxidative stress, a decline in the concentration of mycosporine-glycine was found in both species . Singlet oxygen quenching activity in vitro has also been demonstrated for mycosporine-taurine but evidence for an antioxidative role in vivo is not available so far .
MAAs, although slightly different in their substituents, are a homogenous group of chemical compounds showing strong UV absorption. Marine toxins, in contrast are a structurally diverse group with the common denominator of toxicity. Some of the functions of marine toxins are connected with this characteristic, such as allelopathic effects  and the defence against herbivores . It has been shown that microcystin-LR may exert a phytotoxic effect on aquatic macrophytes  resulting in growth inhibition, reduction in photosynthetic oxygen production and changes in pigment patterns. Detrimental effects of microcystin-RR on other freshwater phytoplankton species have been reported, with growth inhibition, chlorosis, changes in carbohydrate and protein content, among other symptoms . However, no phytotoxic effects of microcystin-LR have been found in the aquatic macrophyte Lemna gibba .
An example of the strong effect of some toxins on grazers has been demonstrated, e.g., in experiments with the toxic dinoflagellate Prorocentrum lima, that produces okadaic acid and nauplii of the shrimp Artemia salina. Artemia cysts incubated in the cell-free culture medium of P. lima hatched, but mortalities were recorded for nauplii that hatched in, and metanuaplii exposed to, test solutions (autoclaved filtered seawater plus cell-free medium) that contained at least 50% of the cell-free medium. Animals exposed to cells of P. lima readily fed on the cells. Some nauplii, especially those just hatched, ingested only one cell before dying, while three days old nauplii ingested up to six cells before dying . Even if the effect of toxins is not lethal to the grazer, toxic species may be avoided. In feeding experiments, the copepod Acartia tonsa was allowed to choose between toxic dinoflagellates (Alexandrium minutum), containing either low or high (up to 2.5 times more) amounts of PSP-toxins, and non-toxic alternative prey. The ingestion of the more toxic dinoflagellates was reduced while the ingestion of the non-toxic alternative remained unchanged .
The toxin domoic acid (DA) plays a role in the uptake of nutrients (Fe and Cu) and possibly the mitigation of Cu toxicity by acting as a chelating agent. The compound is released to the surrounding medium by toxin-producing diatoms under iron-limiting conditions. Fe acquisition improves markedly when DA is artificially added to the medium as well as the effect of Cu toxicity is reduced .
MAAs are reported from almost all algal taxonomic groups examined so far, however, highest concentrations are found in rhodophytes, dinoflagellates, cryptomonads and raphidophytes [51?53]. There are few studies addressing the presence of MAAs and toxins in aquatic organisms at the same time (e.g. ). Nevertheless, a general pattern of co-occurrence of MAAs and toxins in certain groups can be observed.
The occurrence of MAAs is widespread among cyanobacteria, and there are numerous toxin producers in this very old group of microorganisms. Therefore, even if there is a lack in specific studies dealing with UV-absorbing compounds and toxin production simultaneously, it can be postulated that co-occurrence of MAAs and toxins is frequent. The bloom-forming cyanobacterium Microcystis aeruginosa was found to produce the MAAs Porphyra-334 and shinorine, but the presence of toxins in the strain used in the experiments was not tested . Despite the fact that the term ?microcystin? is derived from the genus Microcystis, by far not all Microcystis isolates are toxic. In a study conducted on cyanobacteria from a German lake, individual Microcystis colonies were selected under a microscope, identified and screened for the presence of a gene involved in mycrocystin biosynthesis (mcyB). Most colonies (73%) of Microcystis aeruginosa contained the mcyB gene, whereas only 16% of the colonies assigned to M. ichthyoblabe and no colonies of M. wesenbergii showed the mcyB gene . Another toxin producing genus of cyanobacteria is Nodularia. Not all Nodularia species are toxic, and toxin production seems to occur in the planktonic species Nodularia spumigena, while benthic species are nontoxic . Nodularia spumigena occurs worldwide and is responsible for toxic cyanobacterial blooms e.g. in the Baltic Sea . Three Nodularia species from the Baltic Sea (N. spumigena, N. baltica and N. harveyana) were found to produce the MAAs porphyra-334 and shinorine upon UV-B irradiation . The filamentous bloom-forming cyanobacterium Aphanizomenon flosaquae is marketed today as a food supplement and has been used as a source for the preparation of porphyra-334 . However, strains of this species have been shown to produce PSP toxins, among them saxitoxin .
An extensive screening for the presence of UV-A- and UV-B-absorbing compounds in cultured microalgae (206 strains from 152 species) showed an especially high abundance of UV-absorbing compounds among dinoflagellates, including members of the genera Alexandrium, Amphidinium, Gymnodinium, Heterocapsa, Karlodinium, Kryptoperidinium, Peridinium, Prorocentrum, Scrippsiella, Symbiodinium and Woloszynskia .
Carreto et al.  investigated the composition of pigments, MAAs and PSP toxins (saxitoxin and analogues) in the toxic dinoflagellates Alexandrium tamarense, A. catenella and A. minutum. These bloom forming dinoflagellates accumulate high concentrations of MAAs in varying composition. Toxicity and toxin composition varied widely among the Alexandrium isolates analysed. The toxin contents of A. tamarense and A. catenella were similar (63.2 and 50.5 fmol cell?1) and several times higher than those of A. minutum (1.0 fmol cell?1). Other studies typically concentrate either on MAAs or toxins.
Although not all dinoflagellates produce toxins, many members of this group are notorious for their toxin production. These are often associated with the phenomena commonly called ?red tides?. This term can be quite misleading, because many toxic blooms occur when waters are not discolored while other blooms in which the high biomass and specific pigments of the dinoflagellates turn the water red are not toxic . Blooms of harmful microalgae are now called harmful algal blooms or HABs. Documentation of HABs has expanded greatly over the last few decades, and many efforts are undertaken for better detection by modern techniques 
The marine toxin domoic acid is produced by diatoms of the genera Pseudonitzschia, Amphora and Nitzschia. It was first isolated from the red macroalga Chondria armata and later also found in the red macroalgae Chondria baileyana, Alsidium corallinum, Amansia glomerata, Digenea simplex and Vidalia obtusiloba . Occurrence of MAAs was reported from Pseudonitzschia  and Nitzschia , and from a member of the genus Chondria (Chondria arinata) .
MAA production is primarily stimulated by UV radiation of different wavelength ranges. UV-induced synthesis of MAAs has been reported from cyanobacteria, eukaryotic phytoplankton and macroalgae. In the non toxic dinoflagellate Gyrodinium dorsum, MAA synthesis is induced mainly by radiation around 310 nm, but also considerably by UV-A wavelengths . In the red macroalga Chondrus crispus a monochromatic action spectrum of MAA synthesis showed maximal effects in the UV-A with peaks at 320, 340 and 400 nm . In cyanobacteria UV-B wavelengths are most effective [68,69]. Experiments employing light/dark cycles indicate that in cyanobacteria and algae MAAs are synthesized during the light period. In the rice field cyanobacteria Anabaena sp., Nostoc commune and Scytonema sp. that produce mainly shinorine, a bisubstituted MAA, under natural solar radiation increasing concentrations were found only during the light periods, whereas almost constant values were found at the beginning and the end of the dark period . DCMU, an inhibitor of the photosynthetic electron transport, blocked the synthesis of MAAs in the dinoflagellate Alexandrium excavatum. From this was concluded that MAA synthesis is closely linked to photosynthesis . However, in the cyanobacterium Chlorogloeopsis PCC 6912 MAA synthesis can be induced in the absence of PAR under osmotic stress or artificial UV radiation . Further evidence that photosynthesis is not in all cases essential for the biosynthesis of MAAs comes from the fact that mycosporines are synthesized by fungi , and the single case of a nonphotosynthetic bacterium that is able to produce shinorine, a bisubstituted MAA .
Synthesis of toxins such as cyanobacterial microcystins may also be influenced by light. In Microcystis aeruginosa, microcystin is synthesized nonribosomally via a multifunctional enzyme complex, consisting of both peptide synthetase and polyketide synthase modules coded for by the mcy gene cluster. Both mcyB and mcyD (parts of mcy coding for peptide synthetase and polyketide synthase modules) transcript levels were increased under high light intensities and red light. Blue light and certain artificial stress factors (methylviologen and NaCl) led to reduced transcript amounts. There appeared to be two light thresholds, between dark and low light (16 ?mol of photons m?2 s?1) and between medium (31 ?mol of photons m?2 s?1) and high light (68 ?mol of photons m?2 s?1) at which a significant increase in transcription occurred .
There are pronounced effects of nitrogen supply on the synthesis of MAAs. Nitrogen-limited cultures of the marine dinoflagellates Akashiwo sanguinea (syn. Gymnodinium sanguineum) and Gymnodinium cf. instriatum showed a dramatic decrease in their MAA content when the NO3? concentration in the medium was reduced from 833 ?mol to 25 ?mol (more than threefold) or 5 ?mol (more than sixfold). This decrease was not uniform in all MAAs with mycosporine-glycine, an oxo-MAA (containing only one N atom per molecule in contrast to two N atoms in other MAAs) decreasing least . In the red macroalga Porphyra columbina, addition of ammonium (50 ?M or 250 ?M) to the medium combined with different irradiation treatments led to increased MAA concentrations based on dry weight. The MAA concentration was stimulated most in combination with UV-A plus PAR radiation (29 %) . In the cyanobacterium Anabaena variabilis, application of ammonium to the medium leads to the induction of MAA synthesis in the absence of UV radiation (unpublished observation). Not much is known on the influence of nutrients other than nitrogen on the synthesis of MAAs.
There are also major effects of nutrients on toxin production. In cultures of the toxic dinoflagellate Alexandrium minutum, the production of PSP toxins was greatly enhanced under P-limiting conditions as long as the N supply was sufficient. In stationary-phase cultures the toxin content per cell was greatly increased (more than eightfold) under high N:P ratios (1000:5) as compared to lower N:P ratios. Experiments showed that sufficient protein stocks in the cells are necessary for this dinoflagellate to accumulate high amounts of PSP toxins . As for MAAs, also for the production of PSP toxins the form of N supply has a strong effect. In Alexandrium tamarense, ammonium induced the highest concentration of intracellular toxin, followed by urea and then nitrate. The toxin content was dependent on the cellular N status of nitrate grown cells only, suggesting that the competition for N in toxin production with other metabolic pathways such as growth may be different among N sources .
In the diatom Pseudonitzschia multiseries, production of domoic acid (DA) was enhanced by Fe deficiency and by Cu toxicity. During the exponential phase there was a significant inverse function of cellular growth rates and domoic acid production per cell. Addition of DA to the medium of non toxic diatom strains under Fe deficiency or Cu stress enhanced the uptake of Fe or alleviated the toxicity of Cu, which is in good agreement with the function of DA as a chelating agent . Also under Si and phosphate limitation DA synthesis is increased, and inversely correlated with growth rate [78?80].
In some cyanobacteria MAAs also act as osmoprotectants and are consequently induced by osmotic stress . An influence of temperature on MAA synthesis has also been proposed, because MAA concentrations in field samples correlate with the habitat temperature. However, these temperature differences are coupled to higher incident solar radiation. Experimental evidence on temperature effects is scarce . In contrast to UV and salt stress, neither increased temperature stress nor cold shock induced MAA formation in the cyanobacterium Chlorogloeopsis PCC 6912 .
Whereas the role of optical radiation, especially UV, as the primary elicitor of MAA synthesis is grounded on overwhelming evidence, a similar main factor for toxin synthesis is absent. In addition to nutrient effects, domoic acid production in Pseudonitzschia species may be enhanced by the pH of the surrounding medium. This might, in addition to nutrient limitation, contribute to increased DA production during diatom blooms .
The presence of grazers can induce synthesis of toxins such as gonyautoxins in the dinoflagellate Alexandrium minutum. Waterborne cues from a copepod (Acartia tonsa) induce toxin production in this harmful algal bloom-forming dinoflagellate. Induced A. minutum contained up to 2.5 times more toxins than controls and was more resistant to further copepod grazing .
Marine toxins are transferred through the food chain from the algae producing them to animals feeding on them. Important sources of intoxication in humans are edible shellfish species. During the process of filtration the dinoflagellate cells and cysts are transported to the oesophagus and the stomach of the bivalve molluscs. The digestion takes place in the stomach and the diverticulae. The PSP toxins are released and enter the digestive organs. The particular toxin mixture retained in soft tissues of the shellfish varies in concentration and over time, and is determined by the species and strains of the dinoflagellates and shellfish as well as by other factors like environmental conditions . But also other marine animals such as copepods are able to take up PSP toxins from their food and potentially transmit them to zooplankton-grazing fish, as suggested by high toxin concentrations in the latter .
MAAs are produced by algae and cyanobacteria, but they are also found in corals and other marine life forms including invertebrate and vertebrate animals (e.g. ). As the shikimic acid pathway is the supposed biosynthetic origin of MAAs, these compounds are presumably acquired either by the diet or by endosymbiotic algae . The dietary acquisition and accumulation of MAAs from the diet was confirmed experimentally in the green sea urchin Strongylocentrotus droebachiensis maintained on a controlled diet of the marine red alga Mastocarpus stellatus, rich principally in the MAA shinorine . MAAs were accumulated specifically in the ovaries of this organisms, while in other tissues no differences between the animals fed on a MAA-rich diet and the control animals were found. Embryos of this sea urchin from adults fed an MAA-rich diet showed a significant MAA concentration-dependent protection from UVR-induced cleavage delay compared with those from urchins fed a diet lacking MAAs . Similar feeding experiments were conducted with marine crustaceans species, the amphipod Amphitoe valida and the isopod Idothea baltica, from the mid-littoral of the Patagonia coast (Argentina). These showed a species-specific accumulation behavior in the two organisms. Fed on a diet rich in MAAs, A. valida accumulated higher concentrations of MAAs as compared to I. baltica, and A. valida with high MAA concentrations was found more resistant to UV-B radiation than the same organism with low MAA concentrations . The ability to acquire MAAs from food has also been tested in medaka fish (Oryzias latipes) and in mice, and it was found that the teleost fish was able to acquire MAAs from the diet and accumulate them specifically in the eye, while the mammal was not .
Although details of the biosynthesis of MAAs in marine algae and phototrophic symbioses remain to be demonstrated, it is commonly assumed that they are derived from early steps of the shikimate pathway. Favre-Bonvin et al.  suggested that the shikimate pathway intermediate, 3-dehydroquinate (DHQ), is the precursor for the six-membered carbon ring common to fungal mycosporines (Fig. 1). Synthesis of fungal mycosporines and of MAAs presumably proceeds from DHQ via gadusols (cyclohexenones) (Figure 2) . Other natural compounds containing cyclohexenone rings are ketocarotenoids such as echinenone and canthaxanthin. Echinenone is produced from ?-carotene by the introduction of a keto-group into the ?-ionone ring (for a review see e.g. ). In the mycotoxin griseofulvin from Penicillium griseofulvum, radioactively labeled acetate is incorporated in the cyclohexenone ring structure . In contrast to this neither in the ring structure of fungal mycosporines  nor in that of cyanobacterial MAAs  radioactively labelled acetate is incorporated. Thus it can be assumed that in spite of similar structural features MAA biosynthesis differs fundamenally from ketocarotenoid and griseofulvin biosynthesis.
As for MAAs, the biosynthetic pathways of many marine toxins are not fully understood. Microcystin biosynthesis has been first elucidated in two Microcystis strains [90?92]. The mcy gene cluster in Microcystis encodes six multienzymes that can be assigned to the family of nonribosomal peptide synthetases (NRPS) and type I polyketide synthases (PKS-I), respectively. Nonribosomal peptides (NRP) and polyketides are a structurally diverse group of secondary metabolites that have been identified in a number of prokaryotes and lower eukaryotes .
The structure of the cyanobacterial cyclic peptides are obviously much more complex than those of MAAs, but nevertheless, they share the use of amino acids (or amino alcohols, in the case of some MAAs) as building blocks. The multitude of mycosporines and MAAs is mainly due to different combinations of amino acids or amino alcohols attached at two positions of the central ring (for examples see Fig. 1 A). Thus the function of some (even as yet unknown) enzymes involved in MAA synthesis resembles that of NRPS - they incorporate an amino acid into a larger molecule.
MAAs and marine toxins show a broad overlap in the taxonomic distribution of their occurrence. They are mainly produced by cyanobacteria and algae, and MAAs as well as toxins are transmitted via food chains to organisms of higher trophic levels. In contrast to the transmission of toxins that causes severe adverse effects on animals, so far there is no evidence for any adverse effects of MAAs on any kind of organism. The biosynthetic pathways of many marine toxins and of MAAs are not fully elucidated but MAAs share the use of amino acids as building blocks with the cyclic peptide toxins of cyanobacteria. Further research on the genes involved in MAA synthesis will help to resolve the question of a possible relationship between NRPS and MAA synthesis.
Samples Availability: Available from the authors.
|1.||Lebar MD,Heimbegner JL,Baker BJ. Cold-water marine natural productsNat Prod Rep 2007;24:774–97. [pmid: 17653359]|
|2.||Blunt JW,Copp BR,Hu W-P,Munro MHG,Northcote PT,Prinsep MR. Marine natural productsNat Prod Rep 2007;24:31–86. [pmid: 17268607]|
|3.||Cardozo KHM,Guaratini T,Barros MP,Falc?o VR,Tonon AP,Lopes NP,Campos S,Torres MA,Souza AO,Colepicolo P,Pinto E. Metabolites from algae with economical impactComp Biochem Physiol C Toxicol Pharmacol 2007;146:60–78. [pmid: 16901759]|
|4.||Takano S,Nakanishi A,Uemura D,Hirata Y. Isolation and structure of a 334 nm UV-absorbing substance, porphyra-334 from the red alga Porphyra tenera KjellmanChem Lett 1979;8:419–20.|
|5.||Nakamura H,Kobayashi J,Hirata Y. Separation of mycosporine-like amino acids in marine organisms using reverse-phase high performance liquid chromatographyJ Chromatogr 1982;250:113–18.|
|6.||Bandaranayake WM. Mycosporines: are they nature?s sunscreens? Nat Prod Rep 1998;15:159–72. [pmid: 9586224]|
|7.||Favre-Bonvin J,Bernillon J,Salin N,Arpin N. Biosynthesis of mycosporines: mycosporine glutaminol in Trichothecium roseumPhytochemistry 1987;26:2509–14.|
|8.||Shick JM,Romaine-Lioud S,Ferrier-Pag?s C,Gattuso J-P. Ultraviolet-B radiation stimulates shikimate pathway-dependent accumulation of mycosporine-like amino acids in the coral Stylophora pistillata despite decrease in its population of symbiotic dinoflagellatesLimnol Oceanogr 1999;44:1667–82.|
|9.||Arai T,Nishijima M,Adachi K,Sano H. Isolation and structure of a UV absorbing substance from the marine bacterium Micrococcus sp. AK-334 Marine Biotechnology Institute; Tokyo, Japan: 1992:88–94.|
|10.||Dunlap WC,Shick JM. Ultraviolet radiation-absorbing mycosporine-like amino acids in coral reef organisms: a biochemical and environmental perspectiveJ Phycol 1998;34:418–30.|
|11.||Shick JM,Dunlap WC. Mycosporine-like amino acids and related gadusols: biosynthesis, accumulation, and UV-protective functions in aquatic organismsAnnu Rev Physiol 2002;64:223–62. [pmid: 11826269]|
|12.||Starcevic A,Akthar S,Dunlap WC,Shick JM,Hranueli D,Cullum J. Enzymes of the shikimic acid pathway encoded in the genome of a basal metazoan, Nematostella vectensis, have microbial originsPNAS 2008;105:2533–37. [pmid: 18268342]|
|13.||Klisch M,Sinha RP,Richter PR,H?der D-P. Mycosporine-like amino acids (MAAs) protect against UV-B-induced damage in Gyrodinium dorsum KofoidJ Plant Physiol 2001;158:1449–54.|
|14.||Adams NL,Shick JM. Mycosporine-like amino acids provide protection against ultraviolet radiation in eggs of the green sea urchin Strongylocentrotus droebachiensisPhotochem Photobiol 1996;64:149–58.|
|15.||Neale PJ,Banaszak AT,Jarriel CR. Ultraviolet sunscreens in Gymnodinium sanguineum (Dinophyceae): mycosporine-like amino acids protect against inhibition of photosynthesisJ Phycol 1998;34:928–38.|
|16.||Oren A. Mycosporine-like amino acids as osmotic solutes in a community of halophilic cyanobacteriaGeomicrobiol J 1997;14:231–40.|
|17.||Dunlap WC,Yamamoto Y. Small-molecule antioxidants in marine organisms: antioxidant activity of mycosporine-glycineComp Biochem Physiol B Biochem Mol Biol 1995;112:105–14.|
|18.||Schmid D,Sch?rch C,Z?lli F. UV-A sunscreen from red algae for protection against premature skin agingCosmet Toilet Manufact Worldwide 2004 Yearbook 2004:139–43.|
|19.||Torres A,Enk CD,Hochberg M,Srebnik M. Porphyra-334, a potential natural source for UVA protective sunscreensPhotochem Photobiol Sci 2006;5:432–35. [pmid: 16583025]|
|20.||Bultel-Ponc? V,Felix-Theodore F,Sarthon C,Ponge J-F,Bodo B. New pigments from the terrestrial cyanobacterium Scytonema sp. collected on the Mitaraka Inselberg, French GuyanaJ Nat Prod 2004;67:678–81. [pmid: 15104503]|
|21.||B?del B,Karsten U,Garcia-Pichel F. Ultraviolet-absorbing scytonemin and mycosporine-like amino acids derivatives in exposed rock-inhabiting cyanobacterial lichensOecologia 1997;112:165–72.|
|22.||Bjerke JW,Lerfall K,Elvebakk A. Effects of ultraviolet radiation and PAR on the content of usnic and divaricatic acids in two arctic-alpine lichensPhotochem Photobiol Sci 2002;1:678–85. [pmid: 12665305]|
|23.||Proteau PJ,Gerwick WH,Garcia-Pichel F,Castenholz R. The structure of scytonemin, an ultraviolet sunscreen pigment from the sheaths of cyanobacteriaExperientia 1993;49:825–29. [pmid: 8405307]|
|24.||Cocchietto M,Skert N,Nimis PL,Sava G. A review on usnic acid, an interesting natural compoundNaturwissenschaften 2002;89:137–46. [pmid: 12061397]|
|25.||Garcia-Pichel F,Sherry ND,Castenholz RW. Evidence for an ultraviolet sunscreen role of the extracellular pigment scytonemin in the terrestrial cyanobacterium Chlorogloeopsis spPhotochem Photobiol 1992;56:17–23. [pmid: 1508978]|
|26.||Anon. Marine Biotoxins. Food and Agriculture Organization of the United Nations; Rome, Italy: 2004|
|27.||Daugbjerg N,Hansen G,Larsen J,Moestrup O. Phylogeny of some of the major genera of dinoflagellates based on ultrastructure and partial LSU rDNA sequence data, including the erection of three new genera of unarmoured dinoflagellatesPhycologia 2000;39:302–17.|
|28.||Van Dolah FM. Marine algal toxins: origins, health effects, and their increased occurrenceEnviron Health Perspect 2000;108:133–41. [pmid: 10698729]|
|29.||Chorus I,Bartram J. Toxic cyanobacteria in water, a guide to their public health consequences, monitoring and management. E & FN Spon; London, UK: 1999|
|30.||Vasconcelos V. Cyanobacteria toxins: diversity and ecological effectsLimnetica 2001;20:45–58.|
|31.||Yuan YV,Walsh NA. Antioxidant and antiproliferative activities of extracts from a variety of edible seaweedsFood Chem Toxicol 2006;44:1044–50.|
|32.||Gao K. Chinese studies on the edible blue-green alga, Nostoc flagelliforme: a reviewJ Appl Phycol 1998;10:37–49.|
|33.||Chioccara F,Miscuraca G,Novellino E,Prota G. Occurrence of two new mycosporine-like amino acids, mytilins a and b in the edible mussel, Mytilus galloprovincialisTetrahedron Lett 1979;20:3181–82.|
|34.||Yakovleva I,Takemura A,Bhagooli R,Hidaka M. Differential susceptibility to oxidative stress of two scleractinian corals: antioxidant functioning of mycosporine-glycineComp Biochem Physiol B 2004;139:721–30. [pmid: 15581804]|
|35.||Suh H-J,Lee H-W,Jung J. Mycosporine glycine protects biological systems against photodynamic damage by quenching singlet oxygen with a high efficiencyPhotochem Photobiol 2003;78:109–13. [pmid: 12945577]|
|36.||Oren A,Gunde-Cimerman N. Mycosporines and mycosporine-like amino acids: UV protectants or multipurpose secondary metabolites? FEMS MicrobiolLett 2007;269:1–10.|
|37.||Jokiel PL,York HR. Solar ultraviolet photobiology of the reef coral Pocillopora damicornis and symbiotic zooxanthellaeBull Mar Sci 1982;32:301–15.|
|38.||Shick JM,Lesser MP,Dunlap WC,Stochaj WR,Chalker BE,Wu Won J. Depth-dependent responses to solar ultraviolet radiation and oxidative stress in the zooxanthellate coral Acropora microphthalmaMar Biol 1995;122:41–51.|
|39.||Tartarotti B,Laurion I,Sommaruga R. Large variability in the concentration of mycosporine-like amino acids among zooplankton from lakes located across an altitude gradientLimnol Oceanogr 2001;46:1546–52.|
|40.||Karsten U,Sawall T,Hanelt D,Bischof K,Figueroa FL,Flores-Moya A,Wiencke C. An inventory of UV-absorbing mycosporine-like amino acids in macroalgae from polar to warm-temperate regionsBot Mar 1998;41:443–53.|
|41.||Conde FR,Churio MS,Previtali CM. The deactivation pathways of the excited-states of the mycosporine-like amino acids shinorine and porphyra-334 in aqueous solutionPhotochem Photobiol Sci 2004;3:960–67. [pmid: 15480487]|
|42.||Misonou T,Saitoh J,Oshiba S,Tokitomo Y,Maegawa M,Inoue Y,Hori H,Sakurai T. UV-absorbing substance in the red alga Porphyra yezoensis (Bangiales, Rhodophyta) block thymine photodimer productionMar Biotechnol 2003;5:194–200. [pmid: 12876656]|
|43.||Suh H-J,Lee H-W,Jung J. Singlet oxygen quenching by deoxygadusol and related mycosporine-like amino acids from phytoplankton Prorocentrum micansJ Photosci 2004;11:77–81.|
|44.||Mac?as FA,Galindo JLG,Garc?a-D?az M,Galindo JCG. Allelopathic agents from aquatic ecosystems: potential biopesticides modelsPhytochem Rev 2008;7:155–78.|
|45.||Ajuzie CC. Palatability and fatality of the dinoflagellate Prorocentrum lima to Artemia salinaJ Appl Phycol 2007;19:513–19.|
|46.||Pflugmacher S. Possible allelopathic effects of cyanotoxins, with reference to microcystin-LR, in aquatic ecosystemsEnviron Toxicol 2002;17:407–13. [pmid: 12203964]|
|47.||Hu Z-Q,Liu Y-D,Li D-H. Physiological and biochemical analyses of microcystin-RR toxicity to the cyanobacterium Synechococcus elongatusEnviron Toxicol 2004;19:571–77. [pmid: 15526266]|
|48.||LeBlanc S,Pick FR,Aranda-Rodriguez R. Allelopathic effects of the toxic cyanobacterium Microcystis aeruginosa on duckweed, Lemna gibba LEnviron Toxicol 2005;20:67–73. [pmid: 15712290]|
|49.||Selander E,Thor P,Toth G,Pavia H. Copepods induce paralytic shellfish toxin production in marine dinoflagellatesProc R Soc B Biol Sci 2006;273:1673–80.|
|50.||Maldonado MT,Hughes MP,Rue EL. The effect of Fe and Cu on growth and domoic acid production by Pseudo-nitzschia multiseries and Pseudo-nitzschia australisLimnol Oceanogr 2002;47:515–26.|
|51.||Carreto JI,Carignan MO,Montoya NG. Comparative studies on mycosporine-like amino acids, paralytic shellfish toxins and pigment profiles of the toxic dinoflagellates Alexandrium tamarense, A. catenella and A. minutumMar Ecol Prog Ser 2001;223:49–60.|
|52.||Gr?niger A,Sinha RP,Klisch M,H?der D-P. Photoprotective compounds in cyanobacteria, phytoplankton and macroalgae - a databaseJ Photochem Photobiol B Biol 2000;58:115–22.|
|53.||Jeffrey SW,MacTavish HS,Dunlap WC,Vesk M,Groenewoud K. Occurrence of UVA- and UVB-absorbing compounds in 152 species (206 strains) of marine microalgaeMar Ecol Prog Ser 1999;189:35–51.|
|54.||Liu Z,H?der DP,Sommaruga R. Occurrence of mycosporine-like amino acids (MAAs) in the bloom-forming cyanobacterium Microcystis aeruginosaJ Plankton Res 2004;26:963–66.|
|55.||Kurmayer R,Christiansen G,Chorus I. The abundance of microcystin-producing genotypes correlates positively with colony size in Microcystis sp. and determines its microcystin net production in Lake WannseeAppl Environ Microbiol 2003;69:787–95. [pmid: 12570996]|
|56.||Lyra C,Laamanen M,Lehtim?ki JM,Surakka A,Sivonen K. Benthic cyanobacteria of the genus Nodularia are non-toxic, without gas vacuoles, able to glide and genetically more diverse than planktonic NodulariaInt J Syst Evol Microbiol 2005;55:555–68. [pmid: 15774625]|
|57.||Koskenniemi K,Lyra C,Rajaniemi-Wacklin P,Jokela J,Sivonen K. Quantitative real-time PCR detection of toxic Nodularia cyanobacteria in the Baltic SeaAppl Environ Microbiol 2007;73:2173–79. [pmid: 17277219]|
|58.||Sinha RP,Ambasht NK,Sinha JP,Klisch M,H?der D-P. UV-B-induced synthesis of mycosporine-like amino acids in three strains of Nodularia (cyanobacteria)J Photochem Photobiol B Biol 2003;71:51–58.|
|59.||Pereira P,Onodera H,Andrinolo D,Franca S,Ara?jo F,Lagos N,Oshima Y. Paralytic shellfish toxins in the freshwater cyanobacterium Aphanizomenon flosaquae, isolated from Montargil reservoir, PortugalToxicon 2008;38:1689–702. [pmid: 10858510]|
|60.||Smayda TJ. Harmful algal blooms: their ecophysiology and general relevance to phytoplankton blooms in the seaLimnol Oceanogr 1997;42:1137–57.|
|61.||Babin M,Cullen JJ,Roesler CS,Donaghay PL,Doucette GJ,Kahru M,Scholin CA,Sieracki ME,Sosik HM. New approaches and technologies for observing harmful algal bloomsOceanography 2005;18:210–27.|
|62.||Bates SS. Domoic-acid-producing diatoms: another genus added! JPhycol 2000;36:978–85.|
|63.||Carreto JI,Carignan MO,Montoya NG. A high-resolution reverse-phase liquid chromatography method for the analysis of mycosporine-like amino acids (MAAs) in marine organismsMar Biol 2005;146:237–52.|
|64.||Helbling EW,Chalker BE,Dunlap WC,Holm-Hansen O,Villafa?e VE. Photoacclimation of Antarctic marine diatoms to solar ultraviolet radiationJ Exp Mar Biol Ecol 1996;204:85–101.|
|65.||Karsten U,Sawall T,Wiencke C. A survey of the distribution of UV-absorbing substances in tropical macroalgaePhycol Res 1998;46:271–79.|
|66.||Klisch M,H?der D-P. Wavelength dependence of mycosporine-like amino acid synthesis in Gyrodinium dorsumJ Photochem Photobiol B Biol 2002;66:60–66.|
|67.||Kr?bs G,Watanabe M,Wiencke C. A monochromatic action spectrum for the photoinduction of the UV-absorbing mycosporine-like amino acid shinorine in the red alga Chondrus crispusPhotochem Photobiol 2004;79:515–19. [pmid: 15291302]|
|68.||Portwich A,Garcia-Pichel F. A novel prokaryotic UVB photoreceptor in the cyanobacterium Chlorogloeopsis PCC 6912Photochem Photobiol 2000;71:493–98. [pmid: 10824604]|
|69.||Sinha RP,Sinha JP,Gr?niger A,H?der D-P. Polychromatic action spectrum for the induction of a mycosporine-like amino acid in a rice-field cyanobacterium, Anabaena spJ Photochem Photobiol B Biol 2002;66:47–53.|
|70.||Sinha RP,Klisch M,Helbling EW,H?der D-P. Induction of mycosporine-like amino acids (MAAs) in cyanobacteria by solar ultraviolet-B radiationJ Photochem Photobiol B Biol 2001;60:129–35.|
|71.||Carreto JI,Lutz VA,De Marco SG,Carignan MO. Graneli E,Edler L,Sundstr?m B,Anderson DMToxic Marine Phytoplankton. Elsevier; New York, NY, USA: 1990|
|72.||Leach CM. Ultraviolet-absorbing substances associated with light-induced sporulation in fungiCanad J Bot 1965;43:185–200.|
|73.||Kaebernik M,Brett AN,B?rner T,Dittmann E. Light and the transcriptional response of the microcystin biosynthesis gene clusterAppl Environ Microbiol 2000;66:3387–92. [pmid: 10919796]|
|74.||Litchman E,Neale PJ,Banaszak AT. Increased sensitivity to ultraviolet radiation in nitrogen-limited dinoflagellates: photoprotection and repairLimnol Oceanogr 2002;47:86–94.|
|75.||Peinado NK,D?az RTA,Figueroa FL,Helbling EW. Ammonium and UV radiation stimulate the accumulation of mycosporine-like amino acids in Porphyra columbina (Rhodophyta) from Patagonia, ArgentinaJ Phycol 2004;40:248–59.|
|76.||Touzet N,Franco JM,Raine R. Influence of inorganic nutrition on growth and PSP toxin production of Alexandrium minutum (Dinophyceae) from Cork Harbour, IrelandToxicon 2007;50:106–19. [pmid: 17452045]|
|77.||Leong SCY,Murata A,Nagashima Y,Taguchi S. Variability in toxicity of the dinoflagellate Alexandrium tamarense in response to different nitrogen sources and concentrationsToxicon 2004;43:407–15. [pmid: 15051404]|
|78.||Pan Y,Subba Rao DV,Mann KH,Li WKW,Harrison WG. Effects of silicate limitation on production of domoic acid, a neurotoxin, by the diatom Pseudo-nitzschia multiseries. II. Continuous culture studiesMar Ecol Prog Ser 1996;273:235–43.|
|79.||Pan Y,Subba Rao DV,Mann KH,Brown RG,Pocklington R. Effects of silicate limitation on production of domoic acid, a neurotoxin, by the diatom Pseudo-nitzschia multiseries. I. Batch culture studiesMar Ecol Prog Ser 1996;131:225–33.|
|80.||Pan Y,Subba Rao DV,Mann KH. Changes in domoic acid production and cellular chemical composition of the toxigenic diatom Pseudonitzschia multiseries under phosphate limitationJ Phycol 1996;32:371–81.|
|81.||Lundholm N,Hansen PJ,Kotaki Y. Effect of pH on growth and domoic acid production by potentially toxic diatoms of the genera Pseudonitzschia and NitzschiaMar Ecol Prog Ser 2004;273:1–15.|
|82.||Teegarden GJ,Cemballa AG. Grazing of toxic dinoflagellates, Alexandrium spp., by adult copepods of coastal Maine: implications for the fate of paralytic shellfish toxins in marine food websJ Exp Mar Biol Ecol 1996;196:145–76.|
|83.||Karentz D,McEuen FS,Land MC,Dunlap WC. A survey of mycosporine-like amino acid compounds in Antarctic marine organisms: potential protection from ultraviolet exposureMar Biol 1991;108:157–66.|
|84.||Carroll AK,Shick JM. Dietary accumulation of UV-absorbing mycosporine-like amino acids (MAAs) by the green sea urchin (Strongylocentrotus droebachiensis)Mar Biol 1996;124:561–69.|
|85.||Helbling EW,Menchi CF,Villafa?e VE. Bioaccumulation and role of UV-absorbing compounds in two marine crustacean species from Patagonia, ArgentinaPhotochem Photobiol Sci 2002;1:820–25. [pmid: 12656485]|
|86.||Mason DS,Schafer F,Shick JM,Dunlap WC. Ultraviolet radiation-absorbing mycosporine-like amino acids (MAAs) are acquired from their diet by medaka fish (Oryzias latipes) but not by SKH-1 hairless miceComp Biochem Physiol A Mol Integr Physiol 1998;120:587–98. [pmid: 9828392]|
|87.||Sieiro C,Poza M,de Miguel T,Villa T. Genetic basis of microbial carotenogenesisInt Microbiol 2003;6:11–16. [pmid: 12730708]|
|88.||Lane MP,Nakashima TT,Vederas JC. Biosynthetic source of oxygens in griseofulvin. Spin-echo resolution of 18O isotope shifts in 13C NMR spectroscopyJ Am Chem Soc 1982;104:913–15.|
|89.||Portwich A,Garcia-Pichel F. Biosynthetic pathway of mycosporines (mycosporine-like amino acids) in the cyanobacterium Chlorogloeopsis sp. strain PCC 6912Phycologia 2003;42:384–92.|
|90.||Dittmann E,Neilan BA,Erhard M,von D?hren H,B?rner T. Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in Microcystis aeruginosa PCC 7806Mol Microbiol 1997;26:779–84. [pmid: 9427407]|
|91.||Tillet D,Dittman E,Erhard M,von D?hren H,B?rner T,Neilan BA. Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase systemChem Biol 2000;7:753–64. [pmid: 11033079]|
|92.||Nishizawa T,Ueda A,Asayama M,Fujii K,Harada K,Ochi K,Shirai M. Polyketide synthase gene coupled to the peptide synthetase module involved in the biosynthesis of the cyclic heptapeptide microcystinJ Biochem 2000;127:779–89. [pmid: 10788786]|
|93.||Finking R,Marahiel M. Biosynthesis of nonribosomal peptidesAnnu Rev Microbiol 2004;58:453–88. [pmid: 15487945]|
Keywords: mycosporine-like amino acids, marine toxins, algae, cyanobacteria.
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