Skip to main content
Log in

Cyanobacterial Secondary Metabolite Scytonemin: A Potential Photoprotective and Pharmaceutical Compound

  • Review
  • Published:
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences Aims and scope Submit manuscript

Abstract

Scytonemin is a lipid-soluble, highly stable, yellow–brown-coloured secondary metabolite that is accumulated in the extracellular polysaccharide sheath of several but not all members of cyanobacteria. Chemically, scytonemin is an indole alkaloid composed of two heterocyclic units symmetrically connected through a carbon–carbon bond. Thus, scytonemin is unique among natural products due to its special structure, location in a cell, as well as strong absorption maxima in UV-A in addition to the violet–blue region. Traditionally, scytonemin is a well-established photoprotective compound against ultraviolet radiation. Its accumulation in the cyanobacterial sheath has been suggested to be a strategy adopted by several cyanobacteria to protect their cellular components against damaging effects of UVR. Additionally, recent studies have also established the importance of scytonemin in reactive oxygen species scavenging as well as in controlling the growth of cancerous cells. Thus, scytonemin is both ecologically as well as pharmaceutically important metabolite. Recent developments made in the biochemistry and genetics of this compound have paved the way for its application and commercialization for human welfare. This review aims to present a brief history of the compound with chronological developments made in the study of scytonemin and emphasizes its physiochemistry, analytical chemistry, biochemistry, and genetics. We provide a separate section for metabolic engineering and potential applications of scytonemin, mainly as sunscreen and anti-cancerous drugs. We also discuss the future research directions which need to be worked out.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Garcia-Pichel F, Castenholz RW (1991) Characterization and biological implications of scytonemin, a cyanobacterial sheath pigment. J Phycol 27:395–409

    CAS  Google Scholar 

  2. Pathak J, Sonker AS, Richa R et al (2017) Screening and partial purification of photoprotective pigment, scytonemin from cyanobacteria dominated biological crusts dwelling on the historical monuments in and around Varanasi, India. Microbiol Res (Pavia) 8:6559

    Google Scholar 

  3. Fleming ED, Castenholz RW (2007) Effects of periodic desiccation on the synthesis of the UV-screening compound, scytonemin, in cyanobacteria. Environ Microbiol 9:1448–1455

    CAS  PubMed  Google Scholar 

  4. Fleming ED, Castenholz RW (2008) Effects of nitrogen source on the synthesis of the UV screening compound, scytonemin, in the cyanobacterium Nostoc punctiforme PCC 73102. FEMS Microbiol Ecol 63:301–308

    CAS  PubMed  Google Scholar 

  5. Balskus EP, Case RJ, Walsh CT (2011) The biosynthesis of cyanobacterial sunscreen scytonemin in microbial mat communities. FEMS Microbiol Ecol 77:322–332

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Büdel B, Karsten U, Garcia-Pichel F (1997) Ultraviolet-absorbing scytonemin and mycosporine-like amino acid derivatives in exposed, rock-inhabiting cyanobacterial lichens. Oecologia 112(2):165–172

    PubMed  Google Scholar 

  7. Garcia-Pichel F, Sherry ND, Castenholz RW (1992) Evidence for an ultraviolet sunscreen role of the extracellular pigment scytonemin in the terrestrial cyanobacterium Chlorogloeopsis sp. Photochem Photobiol 56:17–23

    CAS  PubMed  Google Scholar 

  8. Proteau PJ, Gerwick WH, Garcia-Pichel F et al (1993) The structure of scytonemin, an ultraviolet sunscreen pigment from the sheaths of cyanobacteria. Experientia 49:825–829

    CAS  PubMed  Google Scholar 

  9. Simeonov A, Michaelian K (2017) Properties of cyanobacterial UV-absorbing pigments suggest their evolution was driven by optimizing photon dissipation rather than photoprotection. Biol Phys 1–38. arXiv:1702.03588 [physics.bio-ph]

  10. Matsui K, Nazifi E, Hirai Y et al (2012) The cyanobacterial UV-absorbing pigment scytonemin displays radical scavenging activity. J Gen Appl Microbiol 58:137–144

    CAS  PubMed  Google Scholar 

  11. Richter PR, Sinha RP, Häder D-P (2006) Scytonemin-rich epilithic cyanobacteria survive acetone treatment. Curr Trends Microbiol 2:13–19

    Google Scholar 

  12. Garcia-Pichel F, Lombard J, Soule T et al (2019) Timing the evolutionary advent of cyanobacteria and the later great oxidation event using gene phylogenies of a sunscreen. mBio 10(3):e00561-19

    PubMed  PubMed Central  Google Scholar 

  13. Stevenson CS, Capper EA, Roshak AK et al (2002) The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore. J Pharm Exp Ther 303:858–866

    CAS  Google Scholar 

  14. Zhang G, Zhang Z, Liu Z (2013) Scytonemin inhibits cell proliferation and arrests cell cycle through down regulating Plk1 activity in multiple myeloma cells. Tumor Biol 34:2241–2247

    CAS  Google Scholar 

  15. Malla S, Sommer MOA (2014) A sustainable route to produce the scytonemin precursor using Escherichia coli. Green Chem 16:3255–3265

    CAS  Google Scholar 

  16. Rajneesh R, Singh SP, Pathak J et al (2017) Cyanobacterial factories for the production of green energy and value-added products: an integrated approach for economic viability. Renew Sustain Energy Rev 69:578–595

    CAS  Google Scholar 

  17. Chandra R, Iqbal HM, Vishal G et al (2019) Algal biorefinery: a sustainable approach to valorize algal-based biomass towards multiple product recovery. Bioresour Technol 278:346–359

    CAS  PubMed  Google Scholar 

  18. D’Agostino PM, Woodhouse JN, Liew HT et al (2019) Bioinformatic, phylogenetic and chemical analysis of the UV-absorbing compounds scytonemin and mycosporine-like amino acids from the microbial mat communities of Shark Bay, Australia. Environ Microbiol 21(2):702–715

    PubMed  Google Scholar 

  19. Edwards HG, Sadooni F, Vítek P et al (2010) Raman spectroscopy of the Dukhan sabkha: identification of geological and biogeological molecules in an extreme environment. Philos Trans R Soc A Math Phys Eng Sci 368:3099–3107

    CAS  Google Scholar 

  20. Nägeli C (1849) Gattungen einzelliger algen, physiologisch und systematisch bearbeitet. Neue Denkschr. Allg Schweiz Ges Ges Naturwiss 10:1–138

    Google Scholar 

  21. Nägeli C, Schwenderer S (1877) Das Mikroskop, 2nd edn. Willhelm Engelmann Verlag, Leipzig, p 505

    Google Scholar 

  22. Balskus EP, Walsh CT (2010) The genetic and molecular basis for sunscreen biosynthesis in cyanobacteria. Science 329:1653–1656

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim S, Thiessen PA, Bolton EE et al (2016) PubChem substance and compound databases. Nucleic Acids Res 44(D1):D1202–D1213

    CAS  PubMed  Google Scholar 

  24. Bultel-Poncé V, Félix-Théodose F, Sarthou C et al (2004) New pigments from the terrestrial cyanobacterium Scytonema sp. collected on the Mitaraka Inselberg, French Guyana. J Nat Prod 67:678–681

    PubMed  Google Scholar 

  25. Varnali T, Edwards HGM (2010) Ab initio calculations of scytonemin derivatives of relevance to extremophile characterization by Raman spectroscopy. Philos Trans R Soc A Math Phys Eng Sci 368:3099–3107

    Google Scholar 

  26. Grant CS, Louda JW (2013) Scytonemin-imine, a mahogany-colored UV/Vis sunscreen of cyanobacteria exposed to intense solar radiation. Org Geochem 65:29–36

    CAS  Google Scholar 

  27. Varnali T, Edwards HGM (2014) Reduced and oxidised scytonemin: theoretical protocol for Raman spectroscopic identification of potential key biomolecules for astrobiology. Spectrochim Acta A 117:72–77

    CAS  Google Scholar 

  28. Helms GL, Moore RE, Niemczura WP et al (1988) Scytonemin A, a novel calcium antagonist from a blue-green alga. J Org Chem 53:1298–1307

    CAS  Google Scholar 

  29. Lepot K, Compère P, Gérard E et al (2014) Organic and mineral imprints in fossil photosynthetic mats of an East Antarctic lake. Geobiology 12:424–450

    CAS  PubMed  Google Scholar 

  30. Naurin S, Bennett J, Videau P (2016) The response regulator Npun_F1278 is essential for scytonemin biosynthesis in the cyanobacterium Nostoc punctiforme ATCC 29133. J Phycol 52:564–571

    CAS  PubMed  Google Scholar 

  31. Sinclair C, Whitton BA (1977) Influence of nutrient deficiency on hair formation in the rivulariaceae. Br Phycol J 12:297–313

    Google Scholar 

  32. Rath J, Mandal S, Adhikary SP (2012) Salinity induced synthesis of UV-screening compound scytonemin in the cyanobacterium Lyngbya aestuarii. J Photochem Photobiol B Biol 115:5–8

    CAS  Google Scholar 

  33. Kokabi M, Yousefzadi M, Soltani M et al (2019) Effects of different UV radiation on photoprotective pigments and antioxidant activity of the hot‐spring cyanobacterium Leptolyngbya cf. fragilis. Phycol Res. https://doi.org/10.1111/pre.12374

    Article  Google Scholar 

  34. Soule T, Shipe D, Lothamer J (2016) Extracellular polysaccharide production in a scytonemin-deficient mutant of Nostoc punctiforme under UV-A and oxidative stress. Curr Microbiol 73:455–462

    CAS  PubMed  Google Scholar 

  35. Soule T, Stout V, Swingley WD et al (2007) Molecular genetics and genomic analysis of scytonemin biosynthesis in Nostoc punctiforme ATCC 29133. J Bacteriol 189:4465–4472

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Soule T, Palmer K, Gao Q et al (2009) A comparative genomics approach to understanding the biosynthesis of the sunscreen scytonemin in cyanobacteria. BMC Genom 10:336–345

    Google Scholar 

  37. Soule T, Garcia-Pichel F, Stout V (2009) Gene expression patterns associated with the biosynthesis of the sunscreen scytonemin in Nostoc punctiforme ATCC 29133 in response to UV-A radiation. J Bacteriol 191:4639–4646

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Balskus EP, Walsh CT (2008) Investigating the initial steps in the biosynthesis of cyanobacterial sunscreen scytonemin. J Am Chem Soc 130:15260–15261

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Balskus EP, Walsh CT (2009) An enzymatic cyclopentyl[b]indole formation involved in scytonemin biosynthesis. J Am Chem Soc 131:14648–14649

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Matsui D, Asano Y (2019) Creation of thermostable L-tryptophan dehydrogenase by protein engineering and its application for L-tryptophan quantification. Anal Biochem 579:57–63

    CAS  PubMed  Google Scholar 

  41. Gao Q, Garcia-Pichel F (2011) Microbial ultraviolet sunscreens. Nat Rev Microbiol 9:791–802

    CAS  PubMed  Google Scholar 

  42. Rastogi RP, Sonani RR, Madamwar D (2015) Cyanobacterial sunscreen scytonemin: role in photoprotection and biomedical research. Appl Biochem Biotechnol 176:1551–1563

    CAS  PubMed  Google Scholar 

  43. Mushir M, Fatma T (2012) Monitoring stress responses in cyanobacterial scytonemin-screening and characterization. Environ Technol 33:153–157

    CAS  PubMed  Google Scholar 

  44. Dillon JG, Castenholz RW (1999) Scytonemin, a cyanobacterial sheath pigment, protects against UV-C radiation: implications for early photosynthetic life. J Phycol 35:673–681

    CAS  Google Scholar 

  45. Javor B, Castenholz RW (1984) Productivity studies of microbial mats, Laguna Guerrero Negro, Mexico. In: Cohen Y, Castenholz RW, Halvorsan H (eds) Microbial mats: stromatolites. Alan Liss Inc., New York, pp 149–170

    Google Scholar 

  46. Sinha RP, Klisch M, Vaishampayan A et al (1999) Biochemical and spectroscopic characterization of the cyanobacterium Lyngbya sp. inhabiting Mango (Mangifera indica) trees: presence of an ultraviolet-absorbing pigment, scytonemin. Acta Protozool 38:291–298

    CAS  Google Scholar 

  47. Rastogi RP, Incharoensakdi A (2014) Characterization of UV screening compounds, mycosporine-like amino acids, and scytonemin in the cyanobacterium Lyngbya sp. CU2555. FEMS Microbiol Ecol 87:244–256

    CAS  PubMed  Google Scholar 

  48. Muehlstein L, Castenholz RW (1983) Sheath pigment formation in a blue green alga, Lyngbya aestuari, as an adaptation to high light. Biol Bull 165:521–522

    Google Scholar 

  49. Dodds WK (1989) Photosynthesis of two morphologies of Nostoc parmelioides as related to current velocities and diffusion patterns. J Phycol 25:258–262

    Google Scholar 

  50. Chen J, Zhao L, Xu J et al (2013) Determination of oxidized scytonemin in Nostoc commune Vauch cultured on different conditions by high performance liquid chromatography coupled with triple quadrupole mass spectrometry. J Appl Phycol 25:1001–1007

    CAS  Google Scholar 

  51. Itoh T, Koketsu M, Yokota N et al (2014) Reduced scytonemin isolated from Nostoc commune suppresses LPS/IFNc-induced NO production in murine macrophage RAW264 cells by inducing hemeoxygenase-1 expression via the Nrf2/ARE pathway. Food Chem Toxicol 69:330–338

    CAS  PubMed  Google Scholar 

  52. Ehling-Schulz M, Bilger W, Scherer S (1997) UV-B induced synthesis of photoprotective pigments and extracellular polysaccharides in the terrestrial cyanobacterium Nostoc commune. J Bacteriol 179:1940–1945

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Dodds WK, Castenholz RW (1988) The nitrogen budget of an oligotrophic cold water pond. Arch Hydrobiol Suppl 79:343–362

    CAS  Google Scholar 

  54. Rastogi RP, Sinha RP, Incharoensakdi A (2013) Partial characterization, UV-induction and photoprotective function of sunscreen pigment, scytonemin from Rivularia sp. HKAR-4. Chemosphere 93:1874–1878

    CAS  PubMed  Google Scholar 

  55. Asencio AD, Hoffmann L (2013) Chemosystematic evaluation of the genus Scytonema (Cyanobacteria) based on occurrence of phycobiliproteins, scytonemin, carotenoids and mycosporine-like amino acid compounds. Eur J Phycol 48:331–344

    CAS  Google Scholar 

  56. Rastogi RP, Kumari S, Richa, Han T et al (2012) Molecular characterization of hot spring cyanobacteria and evaluation of their photoprotective compounds. Can J Microbiol 58:719–727

    CAS  PubMed  Google Scholar 

  57. Rastogi RP, Incharoensakdi A, Madamwar D (2014) Responses of a ricefield cyanobacterium Anabaena siamensis TISTR-8012 upon exposure to PAR and UV radiation. J Plant Physiol 171:1545–1553

    CAS  PubMed  Google Scholar 

  58. Castenholz RW (1984) Composition of hot-spring microbial mats: a summary. In: Cohen Y, Castenholz RW, Halvorsan H (eds) Microbial mats: stromatolites. Alan R. Liss, Inc., New York, pp 101–119

    Google Scholar 

  59. Ferreira D, Garcia-Pichel F (2016) Mutational studies of putative biosynthetic genes for the cyanobacterial sunscreen scytonemin in Nostoc punctiforme ATCC 29133. Front Microbiol 7:735

    PubMed  PubMed Central  Google Scholar 

  60. Janssen J, Soule T (2016) Gene expression of a two-component regulatory system associated with sunscreen biosynthesis in the cyanobacterium Nostoc punctiforme ATCC 29133. FEMS Microbiol Lett 363:1–6

    Google Scholar 

  61. Klicki K, Ferreira D, Hamill D et al (2018) The widely conserved ebo cluster is involved in precursor transport to the periplasm during scytonemin synthesis in Nostoc punctiforme. mBio 9:e02266-18

    PubMed  PubMed Central  Google Scholar 

  62. Yurchenko T, Ševčíková T, Strnad H et al (2016) The plastid genome of some eustigmatophyte algae harbours a bacteria-derived six-gene cluster for biosynthesis of a novel secondary metabolite. Open Biol 6(11):160249

    PubMed  PubMed Central  Google Scholar 

  63. Edwards HGM, Garcia-Pichel F, Newton EM et al (2000) Vibrational Raman spectroscopic study of scytonemin, the UV-protective cyanobacterial pigment. Spectrochim Acta 56:193–200

    Google Scholar 

  64. Squier AH, Airs RL, Hodgson DA et al (2004) Atmospheric pressure chemical ionisation liquid chromatography/mass spectrometry of the ultraviolet screening pigment scytonemin: characteristic fragmentations. Rapid Commun Mass Spectrom 18:2934–2938

    CAS  PubMed  Google Scholar 

  65. Itoh T, Tsuzuki R, Tanaka T et al (2013) Reduced scytonemin isolated from Nostoc commune induces autophagic cell death in human T-lymphoid cell line Jurkat cells. Food Chem Toxicol 60:76–82

    CAS  PubMed  Google Scholar 

  66. Whitehead K, Hedges JI (2002) Analysis of mycosporine-like amino acids (MAAs) in aquatic plankton by liquid chromatography electrospray-ionization mass spectrometry. Mar Chem 80:27–39

    CAS  Google Scholar 

  67. Varnali T, Gören B (2018) Two distinct structures of the sandwich complex of scytonemin with iron and their relevance to astrobiology. Struct Chem 29:1565–1572

    CAS  Google Scholar 

  68. Edwards HGM, Hutchinson I, Ingley R (2012) The ExoMars Raman spectrometer and the identification of biogeological spectroscopic signatures using a flight-like prototype. Anal Bioanal Chem 404:1723–1731

    CAS  PubMed  Google Scholar 

  69. Venckus P, Paliulis S, Kostkevičiene J et al (2018) CARS microscopy of scytonemin in cyanobacteria Nostoc commune. J Raman Spectrosc 49:1333–1338

    CAS  Google Scholar 

  70. Soule T, Garcia-Pichel F (2014) Ultraviolet photoprotective compounds from cyanobacteria in biomedical applications. In: Sharma NK, Rai AK, Stal LJ (eds) Cyanobacteria: an economic perspective. Wiley, Chichester, pp 119–143

    Google Scholar 

Download references

Acknowledgements

J. Pathak (09/013/0515/2013-EMR-I) and A. Pandey (09/013/0619/2016-EMR-I) are thankful to the Council of Scientific and Industrial Research, New Delhi, India. Rajneesh is grateful to Department of Biotechnology, Govt. of India, (DBT-JRF/13/AL/143/2158), for the grant in the form of senior research fellowships. P.K. Maurya (3616/NET-DEC2014) is thankful to University Grant commission (UGC), New Delhi, India, for financial support in the form of JRF. S.P. Singh acknowledges the UGC for start-up Grant (F.30-370/2017; BSR) and DST-SERB for early career research Award (ECR/2016/000578).

Author information

Authors and Affiliations

Authors

Contributions

JP and SPS conceptualized the idea, did the literature survey, and wrote the paper; Rajneesh, AP, and PM developed the figures and tables; and RPS and SPS edited the manuscript.

Corresponding author

Correspondence to Shailendra P. Singh.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest to publish this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Significance Statement This review highlights the recent advancements made in the study of a cyanobacterial photoprotective compound called scytonemin. The biochemistry and genetics of scytonemin production have been discussed in detail. The roadmap for scytonemin production using metabolically engineered strains and rate-limiting steps for scytonemin biosynthesis have been presented. Also, it emphasizes the various application of scytonemin in different industries for human welfare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pathak, J., Pandey, A., Maurya, P.K. et al. Cyanobacterial Secondary Metabolite Scytonemin: A Potential Photoprotective and Pharmaceutical Compound. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 90, 467–481 (2020). https://doi.org/10.1007/s40011-019-01134-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40011-019-01134-5

Keywords

Navigation