Introduction

There is growing interest in marine organisms to explore the bioactivity of various marine compounds associated with human life. A variety of marine natural products with their specific activities, such as antimalarial, antituberculosis, anticancer, antifoulants, anti-inflammatory, anti-HIV, etc., have been reported from diverse marine organisms such as cyanobacteria, macroalgae, phytoplankton and animals [22, 28]. In recent years, natural products from marine organisms have gained increasing research awareness, and a number of novel marine compounds of potential economic importance have been reported from different marine organisms [22, 60, 61, 111, 123, 216, 230, 231].

During the past 2 decades, a substantial loss in the stratospheric ozone layer has been noticed that has aroused concern about the effects of increased solar ultraviolet radiation (UVR), particularly UV-B radiation (280–315 nm), on the earth’s surface. Solar UV-B radiation is detrimental for most sun-exposed organisms, including humans [84, 88, 187, 192, 193]. An increase in UV-B radiation has aroused interest in searching for the natural photoprotective compounds from various organisms such as microorganisms, plants and animals of marine as well as freshwater ecosystems.

A number of photoprotective compounds, such as melanins, mycosporines, mycosporine-like amino acids (MAAs), scytonemin, parietin, usnic acid, carotenoids, phycobiliproteins, phenylpropanoids and flavonoids and several other UV-absorbing substances of unknown chemical structure, have been identified from different organisms (Fig. 1) [21, 42, 75, 93, 94, 97, 102, 110–112, 124, 194]. There have been a number of reviews about diverse classes of compounds from natural sources including marine habitats, but the occurrence of photoprotectants from marine sources has only partially been elucidated. This review summarizes the occurrence and biosynthesis of important UV-absorbing/screening compounds from various marine sources and their extensive commercial application.

Fig. 1
figure 1

Occurrence of different photoprotective compounds in diverse organisms

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Marine photoprotective compounds

UVR is one of the most harmful exogenous agents and may affect a number of biological functions in all sun-exposed living organisms. Solar radiation exposes the organisms to harmful doses of UV-B and UV-A (315–400 nm) radiation in their natural habitats. In response to intense solar radiation, organisms have evolved certain mechanisms such as avoidance, repair and protection by synthesizing or accumulating a series of photoprotective compounds, such as MAAs, scytonemin, carotenoids and certain other compounds to counteract the toxicity of UV (particularly UV-B) radiation [64, 111, 184, 188, 194, 198]. Furthermore, MAAs are the most common compounds with a potential role as UV sunscreens in marine organisms.

Mycosporine-like amino acids

Mycosporine-like amino acids have been reported in diverse organisms; they are a family of secondary metabolites that directly or indirectly absorb the energy of solar radiation and protect organisms exposed to enhanced solar UVR [84]. MAAs are intracellular, small (<400 Da), colorless and water-soluble compounds that consist of cyclohexenone or cyclohexenimine chromophores conjugated with the nitrogen substituent of amino acids or its imino alcohol [184]. In general, MAAs have a glycine subunit at the third carbon atom, although some MAAs contain sulfate esters or glycosidic linkages through the imine substituents [225]. MAAs are favored as photoprotective compounds because they have maximum UV absorption between 310 and 362 nm, high molar extinction coefficients (ε = 28,100–50,000 M−1 cm−1), the capability to dissipate absorbed radiation efficiently as heat without producing reactive oxygen species (ROS), and photostability and resistance to several abiotic stressors [44, 81, 223].

It has been found that MAAs provide protection from UVR not only for their producers, but also to primary and secondary consumers through the food chain [90]. MAAs have been reported extensively from taxonomically diverse organisms, including many marine groups such as heterotrophic bacteria [4], cyanobacteria and micro/macroalgae. Many animals such as arthropods, rotifers, molluscs, fish, cnidarians, tunicates, eubacteriobionts, poriferans, nemertineans, echinodermates, platyhelminthes, polychaetes, bryozoans and protozoans have also been reported to protect themselves from UVR by MAAs [194]. Recently, an MAA, mycosporine-glycine (MG), has been isolated from the marine lichen Lichina pygmaea [41]. Presently, about 21 MAAs have been reported from terrestrial, freshwater and marine organisms.

High performance liquid chromatography (HPLC) is the common method to detect the particular MAA using the distinctive nature of their retention times and absorption spectra (Fig. 2). However, certain closely related unknown compounds have similar absorption maxima and retention times, which still cause difficulties in the identification process. Liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) can be utilized to examine MAAs' structural diversity [222].

Fig. 2
figure 2

HPDLC chromatograms of some MAAs (a) and their absorption spectra (b)

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MAAs in marine cyanobacteria

Cyanobacteria are prominent in many superficial habitats exposed to high solar irradiance, including intertidal marine flats swamped so infrequently that most eukaryotic competitors and herbivores are absent. On rocky marine substrates, many cyanobacteria form crusts or small cushions in the high intertidal or supratidal zone. They are significant constituents of marine ecosystems and account for a high percentage of oceanic primary productivity. The presence of UV-absorbing compounds like MAAs presumably may have supported the existence of cyanobacteria in the Precambrian era when there was no stratospheric ozone layer. The accumulation of large amounts of MAAs in cyanobacteria was first reported by Shibata [174] from the Great Barrier Reef. Accumulation of MAAs in cells are regulated by an osmotic mechanism that may be evident by the accumulation of high concentrations of MAAs in the field populations of halotolerant cyanobacteria [151]. The probability that MAAs act as UV-B-absorbing compounds has been derived from the fact that the distribution of MAAs in marine organisms shows a significant correlation with depth, which in turn controls the exposure of UV or PAR (photosynthetically active radiation) [57]. Shinorine and porphyra-334 have been found to be the most dominant MAAs in several species of marine cyanobacteria [105, 186, 190] (Table 1). The cyanobacterium Nodularia spumigena is known worldwide for developing toxic blooms, e.g., in the Baltic Sea [116]. Sinha et al. [186] reported three species of this cyanobacterium, Nodularia spumigena, Nodularia baltica and Nodularia harveyana, from the Baltic Sea that produce the MAAs porphyra-334 and shinorine upon UV-B irradiation. MAA-producing cyanobacteria are abundant in hypersaline environments. On the basis of the 16s rRNA gene sequence of 13 MAAs-containing strains of unicellular halophilic cyanobacteria, Garcia-Pichel et al. [73] found a common complement of MAAs in all of them. The majority of halotolerant cyanobacterial populations accumulate high concentrations of MAAs as photoprotective compounds [151].

Table 1 Occurrence of MAAs in some marine cyanobacteria, macroalgae and phytoplankton
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MAAs in marine macroalgae

Several species of macroalgae, belonging to Rhodophyceae (red), Phaeophyceae (brown) and Chlorophyceae (green algae), are used as foodstuffs in the diets of people from Pacific, Asian, Canadian and Icelandic cultures [229]. Besides their food value, many macroalgal species that are commonly exposed to elevated solar radiation synthesize and accumulate high concentrations of MAAs as UV-sunscreen compounds. The presence of UV-absorbing substances in a macroalgal species was first reported by Tsujino and Saito [215]. Later several scientists reported these compounds in all major taxonomic groups [194]. Several species of red algae, such as Acanthophora, Bangia, Bostrychia, Caloglossa, Catenella, Devaleraea, Ceramium, Chondrus, Corallina, Devaleraea, Gelidiella, Gelidium, Gracilaria, Iridea, Palmaria, Phyllophora, Polysiphonia, Porphyra, Stictosiphonia, etc., have been reported to produce high concentrations of different MAAs [194]. Recently, Karsten et al. [103] reported three main MAAs, palythine, shinorine and porphyra-334, from Porphyra umbilicalis isolated from the rocky upper littoral zone of the island Helgoland, Germany, in the North Sea. Six different MAAs, palythine, shinorine, asterina-330, porphyra-334, the medium polarity palythinol, and the low polarity usujirene, have been reported for the first time from the edible red alga, Palmaria palmata (dulse) harvested from the west and east coasts of Grand Manan Island, New Brunswick [230]. Coba et al. [41] recently reported the presence of the MAAs porphyra-334 and shinorine from the red alga Porphyra rosengurttii, asterina-330 and palythine from Gelidium corneum, as well as shinorine from Ahnfeltiopsis devoniensis. Prophyra-334 is an MAA widely distributed among marine algae. The imino-MAAs porphyra-334 and shinorine, isolated from the red alga Gracilaria cornea, have been found to be highly stable against UV and heat stress [189]. Zhaohui et al. [232] reported prophyra-334 from a marine alga that was quite stable in water at a temperature of 60°C. A high degree of MAA diversity has been found in the majority of Rhodophyceae; for instance, Gracilaria changii contains up to seven different UV-absorbing compounds [108].

In contrast to Rhodophyceae the occurrence of MAAs in Chlorophyceae and Phaeophyceae is limited. Within the Chlorophyceae, most species do not contain MAAs or only trace concentrations of these compounds [108]. In an investigation of the occurrence of MAAs in 13 macroalgal Chlorophyceae collected from the intertidal zone of the tropical island Hainan, Karsten et al. [108] found a significant concentration of photoprotective compounds, such as mycosporine-glycine and porphyra-334, only in two green algae, Boodlea composita and Caulerpa racemosa, respectively. Post and Larkum [161] reported certain UV-absorbing compounds of unknown chemical nature from green algae. Han and Han [86] reported the induction of UV-B-absorbing compounds with a prominent absorption maximum at 294 nm in the green alga Ulva pertusa by using different cutoff filters.

Since the occurrence of MAAs is restricted in Chlorophyceae as well as in Phaeophyceae, certain other UV-absorbing compounds might be present in them to protect against UV radiation damage. Pavia et al. [154] reported the occurrence of a polyphenolic compound, phlorotannin, as an UV-absorbing compound (absorbing between 280 and 320 nm) from the brown alga Ascophyllum nodosum. A number of Phaeophyceae produce and accumulate phlorotannins in high concentrations (up to 20% of their dry weight); however, the potential sunscreen functions of phlorotannins need further comprehensive study. Some common macroalgae and their photoprotective products from marine or hypersaline habitats are listed in Table 1.

MAAs in marine phytoplankton/microalgae

Phytoplankton are undoubtedly the major biomass producers in marine ecosystems. In addition to playing a major role in the food web, many genera of phytoplankton produce certain volatile substances such as dimethyl-sulfide (DMS) that serve as an antecedent of cloud condensation nuclei (CCN) and neutralize the greenhouse effect [39]. The cumulative effect of marine biota in the reduction of CO2 concentration and emission of DMS has been estimated to cool the atmosphere by up to 6°C [220]. Like in cyanobacteria and macroalgae, several MAAs (Table 1) have also been isolated and identified from a number of marine phytoplankton species [34, 87, 110, 120, 125, 226]. MAAs have been reported to occur predominantly in members of the Dinophyceae, Bacillariophyceae and Haptophyceae (or Prymnesiophyceae). Some species of dinoflagellates such as Alexandrium excavatum [34] and the prymnesiophyte Phaeocystis pouchetii [133] are known to produce MAAs in high concentrations. It has been found that accumulation of MAAs may occur as a result of UV-induced alterations in the synthesis of amino acids [77]. Elevated levels of PAR (400–700 nm) [34], blue light (400–500 nm) [37], UV-A [37, 63] and UV-B wavelengths [125] have been implicated in the MAA induction response. However, Davidson et al. [49] reported the synthesis of MAAs insensitive to UV-B radiation in five common antarctic diatoms. The dinoflagellate Alexandrium excavatum, isolated from the continental shelf near Buenos Aires shows changes in the MAA composition and an overall increase in UV absorption under low to high PAR [37]. An increase in MAA concentration was shown in the dinoflagellate Prorocentrum micans in the presence of only UV radiation [125]. Photoinduction of MAA synthesis was also found in the dinoflagellate Gyrodinium dorsum in the presence of PAR [110] and only UV-A and UV-B radiation [168]. Time-series data collected at the Bermuda Atlantic time-series study (BATS) site represents the seasonal induction of enhanced UV absorption by MAAs in phytoplankton in the summer-stratified surface water of the Sargasso Sea [142]. In Antarctica, high in vivo absorption at wavelengths indicative of MAAs was characteristic of assemblages dominated by prymnesiophytes [218] and by the chain-forming diatom Thalassiosira gravida [63]. Seasonal variations also affect the MAA concentrations in phytoplankton. Recently, Riemer et al. [169] reported the variation in the concentration of the MAA, mycosporine-glycine and two other UVR-absorbing substances in phytoplankton during different months. UVR-mediated induction of UV-absorbing compounds, with maximal absorption at 334 nm, has recently been observed in Skeletonema costatum, which is a cosmopolitan marine diatom and known as a major component of most red tides in eutrophic regions [224]. It has been suggested that a significant fraction of the UVR reaching the marine diatoms could be absorbed by frustule-bound MAAs. Ingalls et al. [94] for the first time analyzed the diatom frustule-bound organic matter in opal-rich Southern Ocean plankton and sediments and revealed the presence of several MAAs such as palythine, porphyra-334, shinorine as well as traces of asterina-330, palythinol and palythinic acid. The occurrence of MAAs in close association with a mineral phase shows that the mineral matrix can stabilize these compounds and may increase photoprotection against the harmful effects of UVR [94].

MAAs in marine animals

Identification and characterization of different MAAs from various animals such as arthropods, rotifers, molluscs, fishes, cnidarians, tunicates, eubacteriobionts, poriferans, nemertineans, echinodermates, platythelminthes, polychaetes, bryozoans and protozoans has been reported [194]. In nonsymbiotic marine invertebrates, MAAs have been identified in echinoderms, a mussel, a sea hare, brine shrimp and an ascidian [57]. MAAs are common in microalgal-invertebrate symbioses on coral reefs and other habitats [176]. Other than the algal-invertebrate symbioses, there is not much information regarding the occurrence of MAAs in marine alga-bearing protists [57, 176]. However, Sommaruga et al. [198] reported for the first time some photoprotective compounds (shinorine, palythenic acid, palythine, mycosporine-2-glycine and porphyra-334) in a marine algal-bearing ciliate Maristentor dinoferus isolated from coral reefs in Guam, Mariana Islands [130]. A number of MAAs were identified by McClintock and Karentz [136] in 34 species of benthic marine invertebrates. Likewise, in a survey of occurrence of MAAs in marine organisms (48 invertebrates and 1 fish), Karentz et al. [102] accounted for different types of MAAs as photoprotective compounds. The presence of four MAAs, palythine, porphyra-334, asterina-330 and shinorine, and their seasonal variations (summer vs. winter) was investigated in various species of soft corals isolated from the Eastern Red Sea Coast, and palythine was found as the dominant photoprotective compound in Sinularia polydactyla and Sarcophyton trocheliophorum [2]. Concentrations of MAAs vary seasonally and decrease with increasing depth. In most corals there is a positive correlation between MAA concentration and solar UVR [18, 213]. A change in the PAR and UVR components of the solar spectrum with increasing depth significantly affects the primary productivity and the biosynthesis of MAAs in the reef-building coral Montastraea faveolata [126]. Interestingly, MAA concentrations in corals decrease with low water flow and are directly related to rates of photosynthesis [100]. A considerable increase in MAA concentration (up to 67 and 56% for Lobophytum compactum and Sinularia flexibilis, respectively) was shown in female soft corals prior to spawning in comparison to male colonies, which indicates that the parent is providing photoprotectants to its offspring for better survival and furthermore supports the sex-specific variations in levels of photo-protecting mycosporine-like amino acids (MAAs) [137]. At least 14 different MAAs have been characterized in many coral species. Recently, a major novel MAA, palythine-threonine (C12H21N2O6 +) (Fig. 3), has been reported from the hermatypic coral Pocillopora capitata and also from P. eydouxi and Stylophora pistillata [33]. Occurrence of four major MAAs such as mycosporine-taurine, shinorine, porphyra-334, and mycosporine-2 glycine was found in the four sympatric species of sea anemones in the genus Anthopleura collected from intertidal habitats on the Pacific Coast of temperate North America [177]. Moreover, diverse groups of marine animals have been reported to synthesize MAAs (Table 2), which may render organisms more tolerant to oxidative toxicity and increase their survival under the force of stresses such as UVR that mediate production of ROS. It seems that photoprotective compounds are generally produced by the lower photosynthetic organisms including microbes, and marine animals indirectly benefit from the accumulation of MAAs.

Fig. 3
figure 3

Proposed structure of palythine-threonine isolated from the hermatypic coral Pocillopora capitata

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Table 2 Occurrence of MAAs in some marine animals
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Biosynthesis of MAAs

There is still a great deal of controversy concerning the precise mechanisms of MAA biosynthesis. However, it is evident that 3-dehydroquinate formed during the early stages of the shikimate pathway (Fig. 4) serves as a precursor for the synthesis of fungal mycosporines and MAAs via gadusols [176, 184]. The inhibition of MAA synthesis in a hermatypic coral, Stylophora pistillata, by the addition of N-phosphonomethlyglycine (= glyphosate; a specific shikimate pathway inhibitor) has provided the first direct evidence for MAA synthesis through the shikimate pathway in marine organisms [179]. Gadusol (3,5,6-trihydroxy-5-hydroxymethyl-2-methoxycyclohex-2-en-1-one) and deoxygadusol (3,5-dihydroxy-5-hydroxymethyl-2-methoxycyclohex-2-en-1-one) are structurally and biosynthetically related to the MAAs that have been found in roes of cod and other marine fish [40, 156] as well as in eggs, ovaries and larvae of various marine invertebrates [13, 80]. Recently, Singh et al. [183] revealed the probable role of certain genes involved in MAA biosynthesis in cyanobacteria and proposed that the YP_324358 and YP_324357 gene products are involved in the biosynthesis of the common core (deoxygadusol) of all MAAs. The YP_324879 gene product is exclusively involved in the shikimate pathway catalyzing the formation of dehydroquinate, while the YP_324358 gene product in conjunction with the YP_324357 gene product (O-methyltransferase) catalyzes the formation of deoxygadusol, which is the core of all MAAs (Fig. 5).

Fig. 4
figure 4

The supposed biosynthetic routes of MAAs through the shikimate pathway and their possible interconversion. Broken line represents the putative biosynthetic correlation among 3-dehydroquinate, gadusols and MAAs. The steps of the shikimate pathway are represented by thick arrows, and the number (1–7) represents the involvement of seven enzymes that catalyze the sequential steps of the pathway. 1: 3-deoxy-d-arabinoheptulosinate-7-phosphate (DAHP) synthase; 2: dehydroquinate (DHQ) synthase; 3: DHQ dehydratase; 4: shikimate dehydrogenase; 5: shikimate kinase; 6: 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase; 7: chorismate synthase (for details of shikimate pathway, see [176])

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Fig. 5
figure 5

Probable roles of YP 324357 (Ava 3857) and YP 324358 (Ava 3858) genes in the biosynthesis of MAA, shinorine in a cyanobacterium Anabaena variabilis PCC 7937 (modified from [183])

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The synthesis of MAAs is restricted to bacteria, cyanobacteria, phytoplankton and macroalgae and does not occur in animals (metazoa), as they lack the shikimate pathway and take up MAAs via their food. However, recently Starcevic et al. [204] reported the genes encoding enzymes for the shikimate pathway in an animal, the starlet sea anemone Nematostella vectensis, and challenged the universality of this traditional view. Even so, certain marine animals such as arthropods (copepods, krill, sea spiders, isopods, amphipods), molluscs, chordates (fish), cnidarians (sea anemones, jelly fish, corals), protochordates (ascdians), eubacteriobionts, poriferans (sponge), nemertineans (ribbon worm), echinodermates (sea urchins, sea stars, brittle stars, sea cucumbers, sea hares, star fish), crinoids, platyhelminthes (planarian), annelids (polychaetes), bryozoans and protozoans have also been reported to have MAAs [194] derived from their diet or from symbiotic partnerships [57, 140, 148, 169]. Thus, MAAs provide protection from UV radiation not only in their producers, but also to primary and secondary consumers. Richards et al. [166] identified genes involved in all of the steps of the shikimate pathway in both green and red algae (Chlamydomonas reinhardtii and Cyanidoschyzon merolae, respectively) as well as in the diatom Thalassiosira pseudonana.

Mycosporine-glycine is considered as a prime MAA synthesized in the shikimate pathway that further goes through chemical and/or biochemical conversions to produce secondary MAAs (Fig. 4) [29, 36, 45]. Portwich and Garcia-Pichel [160] have observed the specific incorporation of 14C-glycine and 14C-serine into the consequent side chains of mycosporine glycine and shinorine using radiolabelled amino acids, indicating that these free amino acids are their direct precursors. Moreover, it has been assumed that the high diversity of MAAs present in marine organisms is derived from the transformation of mycosporine-glycine, porphyra-334, shinorine and other MAA bisubstituted by amino acids [35, 36, 175]. After irradiation of the toxic dinoflagellate Alexandrium tamarense at photoinhibitory irradiation levels, the concentrations of palythenic acid, usujirene and palythene were found to increase with a simultaneous decrease of the porphyra-334 level [35]. It shows that changes in the level of UVR also play an important role in the interconversions of different MAAs [37]. Recently, Singh et al. [185] also observed the conversion of mycosporine-glycine into two MAAs, porphyra-334 and shinorine, under the influence by PAR and UVR in the cyanobacterium Anabaena doliolum (Fig. 6). Overall, some aspects of the biosynthesis and in particular biotransformations of different MAAs in marine algae and phototropic symbiotic organisms are still unsolved and need more investigation.

Fig. 6
figure 6

Biotransformation of MAAs influenced by PAR and UVR (UV-A, UV-B) radiation in A. doliolum (modified from [185])

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Scytonemin

The photoprotective compound scytonemin is a yellow–brown, lipid-soluble pigment deposited in the exopolysaccharide sheaths of some strains of cyanobacteria inhabiting soil and rock surfaces, barks of trees and marine intertidal mats [71, 72, 162, 170, 191]. This photoprotective pigment was first reported in some terrestrial cyanobacteria [145]. Recently, Richter et al. [167] extracted scytonemin from Lyngbya sp. inhabiting rocks at the shore near Sao Fransisco do Sul, Brasil. It is a dimeric compound composed of indolic and phenolic subunits having a molecular mass of 544 Da (Fig. 7a) and acts as a passive sunscreen in the protection of cyanobacteria against ultraviolet radiation in marine and freshwater environments [162]. The linkage between the two subunits in scytonemin is an olefinic carbon atom that is exclusive among natural products. This complexity of the ring structures of scytonemin generates a specific pattern of UV absorbance [162]. Scytonemin is mainly found in the green oxidized form; however, two other forms of scytonemin such as the oxidized (yellow; e.g., fuscochlorin) and the reduced (red; e.g., fuscorhodin) have been reported to be produced depending on the redox and acid-base conditions during the extraction process [72].

Fig. 7
figure 7

Structure of scytonemin (a) and its absorption spectrum showing a maximum at 386 nm (b)

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Three new pigments, dimethoxyscytonemin, tetramethoxyscytonemin and scytonin (Fig. 8), were recently isolated from the organic extracts of Scytonema sp. They are derived from the scytoneman skeleton of scytonemin. Their structures were allocated principally on the basis of 1H and 13C NMR and MS experiments [27]. Scytonemin has an in vivo absorption maximum at 370 nm, while purified scytonemin has a highest absorption at 386 nm, although it also absorbs significantly at 252, 278 and 300 nm (Fig. 7b), and so it probably helps cyanobacteria to survive lethal UV (UV-A and UV-B) radiation. Scytonemin is the predominant UV-A-photoprotective pigment in the cyanobacterial sheath that reduces the penetration of UV-A radiation into the cell by 90% [72, 74]. It has also been demonstrated that scytonemin alone is sufficient for substantial protection against UV-C damage [53]. It performs its screening activity without any further metabolic investment even after prolonged physiological inactivity; hence, it can be a suitable candidate for use as a natural UV screening compound for humans.

Fig. 8
figure 8

Structures of dimethoxyscytonemin (a), tetramethoxyscytonemin (b) and scytonin (c)

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Biosynthesis of scytonemin

The biosynthesis of scytonemin probably involves tryptophan and tyrosine derivatives that absorb ambient UVR [208]. The biochemical and photoprotective role of scytonemin is well known, and very recently a number of papers about the biosynthesis and molecular genetics of this compound in cyanobacteria have been published [8, 101, 181, 199–202]. A scytonemin-deficient Nostoc punctiforme ATCC 29133 mutant was created using random transposon mutagenesis [202]. The authors found the specific region in the genome of N. punctiforme ATCC 29133 and revealed a cluster of 18 genes, NpR1259–NpR1276, associated with scytonemin biosynthesis (Fig. 9). All 18 genes are co-transcribed as a single transcriptional unit that is upregulated by UV radiation [200]. Based on genetic, biochemical and sequence similarity evidence, Soule et al. [201] illustrated that six putative genes in the scytonemin gene cluster (NpR1276 to NpR1271) with no previously known protein functions are likely involved in the assembly of scytonemin from central metabolites. The assessment of these gene clusters disclosed the occurrence of redundant copies of genes responsible for aromatic amino acid biosynthesis. The evolutionary phylogenetic analysis revealed that the scytonemin gene cluster is distributed across several cyanobacterial lineages, which led to the proposal that the distribution of this gene cluster is best explained by assuming an ancient evolutionary origin [199]. Balskus and Walsh [8] presented the probable biosynthetic route for scytonemin biosynthesis and identified the acyloin reaction as a key step in constructing the carbon framework of this ecologically and evolutionary important pigment. They functionally characterized two enzymes determined by ORFs NpR1275 and NpR1276 from the gene cluster identified by Soule et al. [202], which are involved in the initial step of scytonemin biosynthesis [181] (Fig. 9). NpR1275, which resembles a leucine dehydrogenase, was shown to catalyze the oxidative deamination of tryptophan to form indole-3-pyruvic acid (IPA). IPA, along with the tyrosine precursor p-hydroxyphenylpyruvic acid, acts as the substrate for an acyloin reaction catalyzed by NpR1276 [a homolog to thiamine diphosphate (ThDP)-dependent acetolactate synthase] (Fig. 9). The acyloin product arises from a single β-keto acid regioisomer and exhibits a highly selective reaction by the ThDP-dependent NpR1276 [8]. The products of NpR1263 and NpR1269 ORFs are still to be functionally characterized. From a comparative study of four other cyanobacterial strains, Soule et al. [201] suggested that two supplementary conserved clusters (NpF5232 to NpF5236) and a putative two-component regulatory system (NpF1277 and NpF1278) are possibly involved in scytonemin biosynthesis and regulation, respectively, on the basis of conservation and location.

Fig. 9
figure 9

Proposed biosynthetic pathway for the photoprotective compound scytonemin and associated gene (NpR1259–NpR1276) products. Continuous arrows signify gene products that are functionally characterized, whereas broken arrows indicate the gene products that are still to be functionally characterized for their involvement in subsequent steps. Most of the ORFs in the gene cluster represented by bold arrows from NpR1260–NpR1262, NpR1264–NpR1267 and NpR1269 are predicted to be involved in the biosynthesis of aromatic amino acids while the rests represent ORFs of unknown function (for details, see [200–202])

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Carotenoids

Carotenoids (yellow, orange or red substances) are important components of the photosynthetic apparatus that serve both light-harvesting and photoprotective functions, either as direct quenchers of singlet oxygen and other toxic reactive oxygen species (ROS) or playing a role in the thermal dissipation of excess energy in the photosynthetic apparatus [59, 66, 139, 228]. These are derived from five-carbon isoprene units that are polymerized enzymatically to form regular highly conjugated 40-carbon structures with up to 15 conjugated double bonds. One or both ends of the carbon skeleton may go through cyclization to form ring β-ionone ring end groups, which additionally may be substituted by oxo, hydroxy or epoxy groups at dissimilar positions to form the different xanthophylls [197]. About 600 different carotenoids have been identified from different organisms such as cyanobacteria, bacteria, fungi, phytoplankton, macroalgae, plants and animals [43, 82, 158]. Animals lack the ability to synthesize carotenoids endogenously and thus have to take up these compounds by means of their diet [140]. The pigment astaxanthin, responsible for the pink/red coloration of crustaceans, shellfish and fish such as salmon, is one of the dominant carotenoids found in marine animals by modification of plant carotenoids obtained in the diet.

The role of carotenoids as photoprotective compounds is still controversial to some extent [42]; however, a significant increase (≈50%) in the outer-membrane carotenoids echinenone and myxoxanthophyll was found in the cyanobacterium Nostoc commune after few hours of UV-B irradiation [62]. The photosynthetic activity of the cyanobacterium Synechococcus sp. was found to be more tolerant against UV-B radiation when having increased amounts of endogenous carotenoids caused by genetic manipulation [79]. A small increase in carotenoid content was found in a marine cyanobacterium, Oscillatoria sp. strain BG 091600, after irradiation with UV-A at an irradiance of 10 W/m2 [219]. Carotenoids such as diadinoxanthin, diatoxanthin and β-carotene were found to be induced in phytoplankton under high PAR and UVR [196], and they may play a role in reducing photoinhibition of photosynthesis [25]. Recently, Boulay et al. [24] reported the occurrence and role of the orange carotenoid protein (OCP) in photoprotective mechanisms in various cyanobacteria. Lamare and Hoffman [118] examined the variability in carotenoid concentration in the gonads and eggs of four sea urchin species (Strongylocentrotus purpuratus, S. franciscanus, S. pallidus and S. droebachiensis) to explore the possible role of carotenoids as photoprotective compounds and suggest that carotenoids may serve as photoprotectants against the damaging effects of UV radiation in echinoid eggs.

Photoprotection by the xanthophyll cycle is achieved as a result of dissipation of excess excitation energy as heat [11]. In dinoflagellates, this is mediated by the conversion of diadinoxanthin to diatoxanthin to deactivate excited chlorophyll [3]. Recently, Laurion and Roy [120] have examined the photoprotective role of carotenoids in species of dinoflagellates and diatoms with enhanced ultraviolet-B (UV-B) radiation exposure; they concluded that the xanthophyll cycle is even more important than the protection by MAAs, and the same was observed by Zudaire and Roy [233] for the marine diatom Thalassiosira weissflogii where photoprotective carotenoids (PPCs) dissipate excess energy via the xanthophyll cycle as a long-term UV acclimation response. A significant accumulation of carotenoids was found in the subtidal alga Ptercladiella capillacea after failure of MAA accumulation in response to 1.5–3.0 W m−2 UV-B radiation, which shows that carotenoids are involved in UV-B radiation defense in P. capillacea [124]. The presence or absence of certain carotenoids and their relative concentrations also provide information about the possible acclimation or photoprotection responses of the organisms. The presence of carotenoids implicated in the xanthophyll cycle (XC; conversion of violaxanthin into zeaxanthin via antheraxanthin) indicates the possibility that the organisms might utilize this photoprotection response [173]. In some groups of the Chromophyta, the XC consists of the interconversion of diadinoxanthin into diatoxanthin and thus both cycles are involved in the thermal dissipation of excess light that provides effective photoprotection to the photosynthetic apparatus [121]. Dimier et al. [55] recently described the photoprotective role of XC in marine diatoms. Regarding the biosynthetic pathway of carotenoids in diverse organisms, several studies have recently been published [30, 43, 46, 67]. Figure 10 represents the hypothesized biosynthetic pathway of some carotenoids and showing the XC. In a series of studies Hairston [85] concluded that carotenoids generally function as photoprotectants in high light environments, since carotenoids are antioxidants neutralizing photoproduced radicals [78].

Fig. 10
figure 10

Biosynthetic pathway of some carotenoids. The numbers indicate the enzymes involved in the pathway. Dashed arrows indicate hypothetical conversion steps. GGPP: geranylgeranyl diphosphates, 1: phytoene synthase, 2: phytoene desaturase, 3: ζ-carotene desaturase, 4: carotene isomerase, 5: lycopene α- or β-cyclase, 6: β/ε-ring hydroxylase, 7: β-carotene ketolase, 8: β-carotene 3′3-hydroxylase, 9: zeaxanthin epoxidase, 10: violaxanthin de-epoxidase, 11: violaxanthin de-epoxidase like (based on [31, 43])

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Other marine photoprotective compounds

Besides the occurrence of well-known photoprotective compounds in the marine organisms mentioned above, some other UVR absorbing/screening compounds have been identified in marine organisms including 3-hydroxykynurenine, sporopollenin, melanin and fluorescent pigments. A number of reviews on photoprotective compounds and their protective mechanisms are available that can be referred to for further information in other marine organisms as well as freshwater taxa [9, 42]. Some UV-absorbing compounds such as P380 have been found in the water column near phytoplankton blooms having broad absorbance bands from 300 to 470 nm [128]. Melanin, a complex polymeric structure containing aromatics and indole derivatives, provides UV-A and UV-B screening in humans and many vertebrates [113]. A number of bacteria are reported to produce melanin from phenolic degradation products, such as 3,4-dihydroxyphenylacetate, that accumulate during the catabolism of tyrosine. Tyrosine degradation generally requires multiple catalytic steps to convert tyrosine to melanin precursors [16, 144]. Synthesis of melanin has also been reported from a marine bacterium Shewanella colwelliana [69, 70]. The facultatively anaerobic marine bacterium Shewanella algae produces pyomelanin, but the availability of such soluble compounds in mineralized marine deposits is limited; hence, production of melanin is an important evolutionary adaptation and furthermore, like other organisms, S. algae produces melanin also for the protection from ultraviolet irradiation [157]. Two melanin-generating enzymes, tyrosinase and laccase, with a wide spectrum of activity, have been reported from another marine bacterium Marinomonas mediterranea [131, 172]. Besides the MAAs, large quantities of maristentorin (Fig. 11), a photoreceptor pigment structurally similar to stentorin and hypericin, have recently been reported in a marine ciliate Maristentor dinoferus that may have a protective role against UV irradiation; however, this conclusion needs further evidence [129, 143]. It has been found that the fluorescent pigment granules (FPGs) of corals may supplement the role of MAAs by blocking some of the UV-A [171]. A UV-A-absorbing pigment, biopterin glucoside (BG; a compound chemically related to the pteridine pigments found in butterfly wings) (Fig. 12), with absorption maxima at 256 and 362 nm, has been purified from a marine planktonic cyanobacterium Oscillatoria sp. collected from the coastal areas of Japan [134]. Also Anacystis nidulans, Anabaena variabilis, Nostoc muscorum and Nostoc maseaum were found to produce pteridines in relatively large concentrations. Recently, a compound thalassiolin B (Fig. 13) has been extracted from the marine plant Thalassia testudinum that shows superb antioxidant activity and can efficiently repair UV-B-damaged skin upon its topical application [165]. It has been demonstrated that some seaweed extracts can help to protect skin from UVR [26, 68]. Overall, it seems that our knowledge regarding the assortment and characteristics of UV-absorbing/screening compounds is still in its formative years and much work is still required to elucidate the structure and function of several photoprotective compounds existing in nature.

Fig. 11
figure 11

Possible structures of a pigment maristentorin (a) isolated from marine ciliate Maristentor dinoferus and the structurally related compound stentorin (b) and hypericin (c)

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Fig. 12
figure 12

Structure of the UV-absorbing compound, biopterin glucoside, isolated from the marine planktonic cyanobacterium Oscillatoria sp

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Fig. 13
figure 13

Structure of thalassiolin B isolated from the marine plant Thalassia testudinum

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Effect of environmental factors on the synthesis of photoprotective compounds

Several environmental factors such as different wavelength bands of UVR, desiccation, nutrients, salt concentration, light as well as dark periods have been found to affect the production of photoprotective compounds in various organisms. UVR-induced synthesis of some photoprotective compounds such as MAAs has been reported from diverse cyanobacteria, eukaryotic phytoplankton and macroalgae. In Gyrodinium dorsum, a nontoxic dinoflagellate, MAA was found to increase when induced by 310 nm radiation and also by UV-A radiation [110]. Similarly, a monochromatic action spectrum for photoinduction of the MAA shinorine was found in the red alga Chondrus crispus under UV-A radiation [117]. Photoinduction of MAAs by UVR has been reported in the marine dinoflagellate Scrippsiella sweeneyae and in diatoms [168, 210]. The photoprotective compounds (mainly MAAs and scytonemin) in cyanobacteria are highly responsive to UV-B radiation [190, 195].

It has been found that light is essential for MAA synthesis in cyanobacteria and algae. In an experiment, the circadian induction in MAAs (i.e., increasing during the light period and decreasing during the dark period) was found under alternating light (PAR or PAR + UVR) and dark conditions (Fig. 14) [190]. Furthermore, under natural solar radiation, increasing concentrations of the photoprotective compound shinorine, a bisubstituted MAA, were found only during the light periods, whereas more or less constant values of shinorine concentrations were found during and at the end of the dark period (Fig. 15) [190]. This suggests that synthesis of MAAs is an energy-dependent process and depends on solar energy for its maintenance in natural habitats. However, the role of PAR and photosynthesis in MAAs production is still in dispute, since biosynthesis of MAAs has been reported in the absence of PAR in the cyanobacterium Chlorogloeopsis PCC 6912 [159] as well as in nonphotosynthetic microorganisms such as fungi [122] and the marine bacterium Micrococcus sp. AK-334 [4]. Furthermore, PAR was shown to induce the UV-absorbing compounds in a marine macroalga Chondrus crispus [104] as well as the dinoflagellate Alexandrium excavatum when grown at 200 μmol photons m−2 s−1 as compared to 20 μmol photons m−2 s−1 [37]. Moreover, species of Bangia and Porphyra were found to accumulate UV-absorbing compounds not only in their natural environments, but also under long-term low-light laboratory conditions [92, 109]. The effect of different light qualities (white, blue, green, yellow and red light) on the accumulation of particular MAAs has also been observed. Korbee et al. [114] reported the favorable role of blue light in the accumulation of the MAAs porphyra-334, palythine and asterina-330, while shinorine was found to accumulate under white, green, yellow and red light in Porphyra leucosticta isolated from the intertidal zone of Lagos, Málaga, Southern Spain.

Fig. 14
figure 14

UV-B radiation-induced circadian induction of MAAs in cyanobacteria showing the distinct induction in the light phase (L) and no induction in dark phase (D). UV-A and PAR show only low level MAA induction relative to UV-B (adapted from [190])

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Fig. 15
figure 15

Absorption spectra of the cells showing the induction of MAAs by UV-B (295 cut-off filter) radiation in a cyanobacterium Nostoc commune after different durations of irradiation. Cells were exposed under natural solar radiation, and aliquots were withdrawn at alternating light (4, 8, 24, 32 and 56 h) and dark (48 and 72 h) periods. The results show that MAAs were induced only during light periods, and during dark incubation the concentration of MAAs either remained as such or declined slightly (adapted from [190])

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Nutrient conditions also affect the biosynthesis of MAAs to a great extent. A remarkable decrease in MAA content was found in the marine dinoflagellates Akashiwo sanguinea (syn. Gymnodinium sanguineum) and Gymnodinium cf. instriatum under reduced nitrogen concentration [127]. Enriched ammonium concentrations have been shown to raise the contents of UV-absorbing compounds in the red macroalga Porphyra sp. [115, 155]. Recently, Singh et al. [182] also reported the induction of MAA synthesis by salt and ammonium in a concentration-dependent manner without UV stress in the cyanobacterium Anabaena variabilis PCC 7937.

Certain other factors such as osmotic stress, salt stress as well as temperature have also been found to affect the biosynthesis of MAAs in some cyanobacteria [159, 182, 189]. Portwich and Garcia-Pichel [159] have reported the induction of MAA synthesis by salt stress without PAR or UV radiation in the cyanobacterium Chlorogloeopsis sp. PCC 6912, which can live on up to 70% sea water salinity. Little is known concerning the effect of desiccation on the concentration of UV-absorbing/screening compounds of intertidal species that are often exposed and desiccated during low tides, though it has been investigated in other studies carried out with bryophytes, grass and lichens [132, 150] as well as cyanobacteria [64]. However, recently, Jiang et al. [99] reported the role of desiccation in maintaining a high concentration of UV-absorbing compounds in an intertidal red alga Porphyra haitanensis. The local climatic conditions also affect the concentrations of MAAs in a particular organism. Karsten et al. [104] demonstrated that the concentrations of MAAs in Rhodophyceae from polar (Spitsbergen) and cold-temperate (Helgoland, North Sea) regions are usually only half of those in species from warm-temperate (Spain) localities. In marine organisms MAA levels also depend on depth, since most species of Rhodophyceae growing in deeper waters lack these compounds. In Polysiphonia arctica growing in the subtidal zone of Spitsbergen, a strong decrease in MAA concentration with increasing depth (1–7 m) has been found [104]. Thus, it may be concluded that lower MAA contents in species from higher latitudes or from deeper waters correlate with lower natural solar UV irradiances in the respective habitat.

The biosynthesis of scytonemin is strongly induced by UV-A and PAR at high photon fluence rates [72]. The effect of light quality has also been examined, and it has been found that UV-A treatment is very efficient in inducing scytonemin synthesis, whereas blue, green or red light at the same fluence rates does not cause any significant increase in scytonemin [72]. Dillon et al. [54] investigated the effect of other correlated stress factors including heat, osmotic and oxidative stress on the synthesis of scytonemin in the cyanobacterium Chroococcidiopsis sp. and showed that both increases in temperature and oxidative stress in combination with UV-A have a synergistic effect on high production of scytonemin. Recently, Fleming and Castenholz [65] have shown the effects of nitrogen sources on scytonemin synthesis in the cyanobacterium Nostoc punctiforme PCC 73102. Thus, scytonemin induction may be regulated as a part of a complex stress response pathway in which multiple environmental signals affect its synthesis.

In a study of the seasonal pigment pattern of surface phytoplankton, Barlow et al. [14] found that under low temperature and irradiance conditions, the photosynthetic carotenoids were prominent; however, as temperatures and irradiance increased and nutrients declined, there was a significant increase in the proportion of photoprotective carotenoids. High levels (≈80% of total carotenoids) of photosynthetic carotenoids (PSCs) have been reported in high-productivity ecosystems dominated by large phytoplankton in contrast to low-chlorophyll surface waters with prominent small cells, where photoprotective carotenoids (PPCs) were dominant with >70% of the total carotenoid pool [15, 76]. These differences might be due to physiological responses to the variability in the environmental conditions [15, 76, 217]. Overall, it seems that MAAs have different signal transduction pathways (e.g., biochemical as well as photosensory and genetical) for the synthesis of MAAs; however, not much is known regarding the biosynthesis of MAAs, and further work is required to establish this assumption.

Photoprotective compounds: commercial applications

UVR is one of the major exogenous harmful factors to human health [52]. Photoprotective compounds such as MAAs, scytonemin, carotenoids and some other substances, identified in a wide variety of marine organisms, have anti-inflammatory and antioxidant properties with possible applications in the cosmetic and pharmaceutical industries [164]. MAAs with high absorption in the UV region can potentially be used in cosmetics and toiletries as UV protectors and activators of cell proliferation [44, 176, 214, 223]. The MAAs such as shinorine (SH), porphyra-334 (P-334) and mycosporine-glycine have potentials to protect the fibroblast cells from UVR-induced cell death [153]. The combined action of P-334 and shinorine, extracted from the red alga Porphyra umbilicalis, has been reported to suppress UV-induced aging in human skin [48]. MAAs exhibit a high antioxidant activity scavenging superoxide anions and inhibiting lipid peroxidation [50, 51] resulting from UV-induced production of ROS [152, 209]. Recently, Coba et al. [41] also reported the antioxidant activity of P-334 and shinorine from Porphyra and other red algae, maintaining the antioxidant defense system of the skin as well as Hsp70 expression. The antioxidant activities of the MAAs glycine and usujilene have been reported to inhibit lipid peroxidation in aqueous extracts of marine organisms and to scavenge 1O2 generated from certain endogenous photosensitizers [147, 209]. Yoshiki et al. [227] reported a new antioxidant compound from the MAA porphyra-334 by heat treatment. MAAs can block the production of both 6–4 photoproduct and cyclobutane pyrimidine dimer (CPD) formation [138]. Certain synthetic analogues of MAAs, such as tetrahydropyridine derivatives, have been developed for commercial application as suncare products [19, 38, 56]. Moreover, a product called Helioguard® 365 that contains mycosporine-like amino acids from the red alga Porphyra umbilicalis has been commercialized [31]. Besides the production of sun care products, MAAs have been commercially explored in the manufacture of several non-biological materials such as photostabilizing additives in plastics, paints and varnishes [12].

Scytonemin has dual kinase inhibitory activity that may be therapeutically important in acute and possibly chronic disorders of inflammation and proliferation. In human T-cell leukemia Jurkat cells, scytonemin repressed cell proliferation (IC50 = 7.8 μM) and induced apoptosis in 24% of the cells (at 3 μM). Scytonemin showed a concentration-dependent inhibition of phosphorylation of cdc25C mediated by a polo-like kinase 1 (PLK1) and plays a significant role in regulating the G2/M transition in the cell cycle [205]. The cyclic peptide scytonemin A from Scytonema sp. has been shown to be a calcium agonist [91]. Overall, scytonemin has immense pharmacological potential with antiinflammatory and antiproliferative activities [206] that could be used to build up several novel classes of therapeutically valuable drugs.

Carotenoids may also directly provide photoprotection against UVR-induced photooxidation in the skin and also provide protection against inflammation, ulcers due to Helicobacter pylori infection and age-related diseases [7, 17, 31, 83, 180]. It has been shown that β-carotene can modulate UV-A-induced gene expression in human keratinocytes [221]. Carotenoids have also been assessed in relation with their antioxidant properties [47] that can play a key role in reducing the incidence of several UVR-mediated diseases [6]. Several commercial values of carotenoids such as natural food coloring agents, food additives, drugs, enhancers of the color of egg yolks, improving the health and fertility of cattle, and use in the cosmetic industries have been reported [98, 203]. Arbeloa et al. [5] reported the occurrence of natural antioxidant gadusol (3,5,6-trihydroxy-5-hydroxymethyl-2-methoxycyclohex-2-en-1-one) in fish roes from the Argentine Sea and found that Brazilian sandperch (Pinguipes brasilianus) and Argentinian sandperch (Pseudopercis semifasciata) are useful sources of antioxidants for human consumption. Some carotenoids offer provitamin A activity [135], and high consumption of carotenoids may diminish threats of certain pathologies [211]. Overall, it seems that these photoprotective compounds may be of immense value in future biotechnological research for the production of a number of commercial products directly related to human health.

Conclusions

Synthesis and/or accumulation of a number of photoprotective compounds has been recognized from diverse groups of marine organisms that may counteract several structural as well as physiological damages caused by UVR. MAAs are the imperative and ubiquitous group of sunscreen compounds in a large number of marine organisms that can potentially reduce the detrimental effects of UVR. Besides MAAs, scytonemin, carotenoids and several other compounds have also been found to play a significant role in mitigating the toxic effects of UVR in a number of marine organisms. The concentrations of photoprotective compounds in organisms are often positively correlated with the exposure to UV-R and other exogenous factors. Moreover, these photoprotective compounds have several other potential functions with therapeutic properties that may be exploited in a large amount of commercial applications, and further development of marine biotechnology for human photoprotection and research must be specially focused on the analysis, biosynthesis and mode of action of several unknown photoprotective compounds against several abnormalities induced by UVR.