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The paradox of cyanotoxins: from natural toxins to biotechnological resources

Authors

DOI:

https://doi.org/10.62063/rev-32

Keywords:

bioactivity, biotechnological applications, cyanobacteria, cyanotoxins, microcystins

Abstract

Cyanotoxins are highly toxic secondary metabolites produced by cyanobacteria that decrease water quality and exert a wide range of harmful effects on many organisms, including humans, through the food web. For many years, cyanotoxins were examined solely for their toxic effects; however, ongoing molecular biology, biochemistry, and applied biotechnology research on these metabolites has contributed to reframing them as valuable natural compounds in medicine, agriculture, and environmental biotechnology. Cyanotoxins exhibit anticancer, antimicrobial, allelopathic, and biopesticidal activities, providing promising opportunities for novel therapeutics, sustainable agriculture, and enhanced environmental remediation. Nevertheless, their high toxicity, potential harmful effects on non-target organisms, and environmental persistence necessitate comprehensive safety evaluations, environmental risk assessments, and the development of controlled application strategies. This review aims to highlight the ecological and biotechnological significance of cyanotoxins and seeks to stimulate further investigations into these natural metabolites as promising candidates for future sustainable technological developments.

References

Abe, T., Unno, M., Onogawa, T., Tokui, T., Kondo, T. N., Nakagomi, R., Adachi, H., Fujiwara, K., Okabe, M., Suzuki, T., Nunoki, K., Sato, E., Kakyo, M., Nishio, T., Sugita, J., Asano, N., Tanemoto, M., Seki, M., Date, F., Ono, K., Kondo, Y., Shiiba, K., Suzuki, M., Ohtani, H., Shimosegawa, T., Iinuma, K., Nagura, H., Ito, S., & Matsuno, S. (2001). LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology, 120(7), 1689–1699. https://doi.org/10.1053/gast.2001.24804 DOI: https://doi.org/10.1053/gast.2001.24804

Akmukhanova, N. R., Leong, Y. K., Seiilbek, S. N., Konysbay, A., Zayadan, B. K., Sadvakasova, A. K., Sarsekeyeva, F. K., Bauenova, M. O., Bolatkhan, K., Alharby, H. F., Chang, J.-S., & Allakhverdiev, S. I. (2023). Eco-friendly biopesticides derived from CO₂-fixing cyanobacteria. Environmental Research, 239, 117419. https://doi.org/10.1016/j.envres.2023.117419 DOI: https://doi.org/10.1016/j.envres.2023.117419

Almeida, É. C., Jacinavicius, F. R., Médice, R. V., Menezes, R. B., Passos, L. S., Anderson, D., Yoon, J., Faria, E. D., Crnkovic, C. M., Fonseca, A. L., Henry, T., & Pinto, E. (2025). Unraveling the toxicity of a non-microcystin-producing strain (CCIBt3106) of Microcystis aeruginosa: Ecotoxicological effects on aquatic invertebrates. Toxins, 17(7), 321. https://doi.org/10.3390/toxins17070321 DOI: https://doi.org/10.3390/toxins17070321

Ayilara, M. S., Adeleke, B. S., Akinola, S. A., Fayose, C. A., Adeyemi, U. T., Gbadegesin, L. A., Omole, R. K., Johnson, R. M., Uthman, Q. O., & Babalola, O. O. (2023). Biopesticides as a promising alternative to synthetic pesticides: A case for microbial pesticides, phytopesticides, and nanobiopesticides. Frontiers in Microbiology, 14, 1040901. https://doi.org/10.3389/fmicb.2023.1040901 DOI: https://doi.org/10.3389/fmicb.2023.1040901

Berry, J. P., Gantar, M., Perez, M. H., Berry, G., & Noriega, F. G. (2008). Cyanobacterial toxins as allelochemicals with potential applications as algaecides, herbicides and insecticides. Marine Drugs, 6(2), 117–146. https://doi.org/10.3390/md20080007 DOI: https://doi.org/10.3390/md6020117

Bittencourt-Oliveira, M. C., Chia, M. A., de Oliveira, H. S. B., Araújo, M. K. C., Molica, R. J. R., & Dias, C. T. S. (2015). Allelopathic interactions between microcystin-producing and non-microcystin-producing cyanobacteria and green microalgae: Implications for microcystins production. Journal of Applied Phycology, 27, 275–284. https://doi.org/10.1007/s10811-014-0326-2 DOI: https://doi.org/10.1007/s10811-014-0326-2

Bláha, L., Babica, P., & Maršálek, B. (2009). Toxins produced in cyanobacterial water blooms – toxicity and risks. Interdisciplinary Toxicology, 2(2), 36–41. https://doi.org/10.2478/v10102-009-0006-2 DOI: https://doi.org/10.2478/v10102-009-0006-2

Bojadžija Savić, G., Bormans, M., Edwards, C., Lawton, L., Briand, E., & Wiegand, C. (2020). Cross talk: Two-way allelopathic interactions between toxic Microcystis and Daphnia. Harmful Algae, 94, 101803. https://doi.org/10.1016/j.hal.2020.101803 DOI: https://doi.org/10.1016/j.hal.2020.101803

Cock, I. E., & Cheesman, M. J. (2023). A review of the antimicrobial properties of cyanobacterial natural products. Molecules, 28(20), 7127. https://doi.org/10.3390/molecules28207127 DOI: https://doi.org/10.3390/molecules28207127

Cui, Y., König, J., Nies, A. T., Pfannschmidt, M., Hergt, M., Franke, W. W., Alt, W., Moll, R., & Keppler, D. (2003). Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma. Laboratory Investigation, 83(4), 527–538. https://doi.org/10.1097/01.lab.0000065015.02412.48 DOI: https://doi.org/10.1097/01.LAB.0000065015.02412.48

Cycoń, M., Mrozik, A., & Piotrowska-Seget, Z. (2017). Bioaugmentation as a strategy for the remediation of pesticide-polluted soil: A review. Chemosphere, 172, 52–71. https://doi.org/10.1016/j.chemosphere.2016.12.129 DOI: https://doi.org/10.1016/j.chemosphere.2016.12.129

da Silva Pinto Neto, J., Serra, G. M., Xavier, L. P., & Santos, A. V. (2025). Chemodiversity and biotechnological potential of microginins. International Journal of Molecular Sciences, 26(13), 6117. https://doi.org/10.3390/ijms26136117 DOI: https://doi.org/10.3390/ijms26136117

Demay, J., Bernard, C., Reinhardt, A., & Marie, B. (2019). Natural products from cyanobacteria: Focus on beneficial activities. Marine Drugs, 17(6), 320. https://doi.org/10.3390/md17060320 DOI: https://doi.org/10.3390/md17060320

Du, X., Liu, H., Yuan, L., Wang, Y., Ma, Y., Wang, R., Chen, X., Losiewicz, M. D., Guo, H., & Zhang, H. (2019). The diversity of cyanobacterial toxins on structural characterization, distribution and identification: A systematic review. Toxins, 11(9), 530. https://doi.org/10.3390/toxins11090530 DOI: https://doi.org/10.3390/toxins11090530

Durai, P., Batool, M., & Choi, S. (2015). Structure and effects of cyanobacterial lipopolysaccharides. Marine Drugs, 13(7), 4217–4230. https://doi.org/10.3390/md13074217 DOI: https://doi.org/10.3390/md13074217

Falfushynska, H., Horyn, O., Osypenko, I., Rzymski, P., Wejnerowski, Ł., Dziuba, M. K., & Sokolova, I. M. (2021). Multibiomarker-based assessment of toxicity of central European strains of filamentous cyanobacteria Aphanizomenon gracile and Raphidiopsis raciborskii to zebrafish Danio rerio. Water Research, 194, Article 116923. https://doi.org/10.1016/j.watres.2021.116923 DOI: https://doi.org/10.1016/j.watres.2021.116923

Fischer, W. J., Altheimer, S., Cattori, V., Meier, P. J., Dietrich, D. R., & Hagenbuch, B. (2005). Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicology and Applied Pharmacology, 203(3), 257–263. https://doi.org/10.1016/j.taap.2004.08.012 DOI: https://doi.org/10.1016/j.taap.2004.08.012

Ger, K. A., Faassen, E. J., Pennino, M. G., & Lürling, M. (2016). Effect of the toxin (microcystin) content of Microcystis on copepod grazing. Harmful Algae, 52, 34–45. https://doi.org/10.1016/j.hal.2015.12.008 DOI: https://doi.org/10.1016/j.hal.2015.12.008

Giannuzzi, L., Sedan, D., Echenique, R., & Andrinolo, D. (2011). An acute case of intoxication with cyanobacteria and cyanotoxins in recreational water in Salto Grande Dam, Argentina. Marine Drugs, 9(11), 2164–2175. https://doi.org/10.3390/md9112164 DOI: https://doi.org/10.3390/md9112164

Haque, F., Banayan, S., Yee, J., & Chiang, Y. W. (2017). Extraction and applications of cyanotoxins and other cyanobacterial secondary metabolites. Chemosphere, 183, 164–175. https://doi.org/10.1016/j.chemosphere.2017.05.106 DOI: https://doi.org/10.1016/j.chemosphere.2017.05.106

Holland, A., & Kinnear, S. (2013). Interpreting the possible ecological role(s) of cyanotoxins: Compounds for competitive advantage and/or physiological aide? Marine Drugs, 11(7), 2239–2258. https://doi.org/10.3390/md11072239 DOI: https://doi.org/10.3390/md11072239

Kaebernick, M., & Neilan, B. A. (2001). Ecological and molecular investigations of cyanotoxin production. FEMS Microbiology Ecology, 35(1), 1–9. https://doi.org/10.1111/j.1574-6941.2001.tb00782.x DOI: https://doi.org/10.1111/j.1574-6941.2001.tb00782.x

Kaštovský, J., Hauer, T., Mareš, J., & Johansen, J. R. (2024). Welcome to the jungle!: An overview of modern taxonomy of cyanobacteria. Hydrobiologia, 851, 1063–1077. https://doi.org/10.1007/s10750-023-05356-7 DOI: https://doi.org/10.1007/s10750-023-05356-7

Kiviranta, J., Abdel-Hameed, A., Sivonen, K., Niemelä, S. I., & Carlberg, G. (1993). Toxicity of cyanobacteria to mosquito larvae—Screening of active compounds. Environmental Toxicology and Water Quality, 8(1), 63–71. https://doi.org/10.1002/tox.2530080107 DOI: https://doi.org/10.1002/tox.2530080107

Kurmayer, R., & Christiansen, G. (2009). The genetic basis of toxin production in cyanobacteria. Freshwater Reviews, 2(1), 31–50. https://doi.org/10.1608/FRJ-2.1.2 DOI: https://doi.org/10.1608/FRJ-2.1.2

Lee, V., Zheng, S., Meza-Padilla, I., & Nissimov, J. I. (2023). The curious case of cyanobacteria: A tale of light and darkness [Preprint]. bioRxiv. https://doi.org/10.1101/2023.05.16.541008 DOI: https://doi.org/10.1101/2023.05.16.541008

Lee, W., Belkhiri, A., Lockhart, A. C., Merchant, N., Glaeser, H., Harris, E. I., Washington, M. K., Brunt, E. M., Zaika, A., Kim, R. B., & El-Rifai, W. (2008). Overexpression of OATP1B3 confers apoptotic resistance in colon cancer. Cancer Research, 68(24), 10315–10323. https://doi.org/10.1158/0008-5472.CAN-08-1984 DOI: https://doi.org/10.1158/0008-5472.CAN-08-1984

Li, K., Yang, M., Dai, Y., Huang, J., Zhu, P., & Liu, Q. (2024). Microcystin-LR improves anti-tumor efficacy of oxaliplatin through induction of M1 macrophage polarization. Toxicon, 247, 107796. https://doi.org/10.1016/j.toxicon.2024.107796 DOI: https://doi.org/10.1016/j.toxicon.2024.107796

Li, Z., Zhu, X., Wu, Z., Sun, T., & Tong, Y. (2023). Recent advances in cyanotoxin synthesis and applications: A comprehensive review. Microorganisms, 11(11), 2636. https://doi.org/10.3390/microorganisms11112636 DOI: https://doi.org/10.3390/microorganisms11112636

Lyons, T. W., Reinhard, C. T., & Planavsky, N. J. (2014). The rise of oxygen in Earth’s early ocean and atmosphere. Nature, 506(7488), 307–315. https://doi.org/10.1038/nature13068 DOI: https://doi.org/10.1038/nature13068

Magonono, M., Oberholster, P. J., Shonhai, A., Makumire, S., & Gumbo, J. R. (2018). The presence of toxic and non-toxic cyanobacteria in the sediments of the Limpopo River Basin: Implications for human health. Toxins, 10(7), 269. https://doi.org/10.3390/toxins10070269 DOI: https://doi.org/10.3390/toxins10070269

Martínez-Burgos, J., Pozzan, R., Aguiar Severo, I., & Ordonez, J. C. (2024). Introductory chapter: Cyanobacteria – an overview. In Insights into Algae – Fundamentals, Culture Techniques and Biotechnological Uses of Microalgae and Cyanobacteria. IntechOpen. https://doi.org/10.5772/intechopen.1004953 DOI: https://doi.org/10.5772/intechopen.1004953

Marumure, J., Gwenzi, W., Makuvara, Z., Simbanegavi, T. T., Alufasi, R., Goredema, M., Gufe, C., Karidzagundi, R., Rzymski, P., & Halabowski, D. (2025). Global occurrence of cyanotoxins in drinking water systems: Recent advances, human health risks, mitigation, and future directions. Life, 15(5), 825. https://doi.org/10.3390/life15050825 DOI: https://doi.org/10.3390/life15050825

McCluskey, A., Sim, A. T. R., & Sakoff, J. A. (2002). Serine–threonine protein phosphatase inhibitors: Development of potential therapeutic strategies. Journal of Medicinal Chemistry, 45(6), 1151–1175. https://doi.org/10.1021/jm010066k DOI: https://doi.org/10.1021/jm010066k

Mehdizadeh Allaf, M., & Peerhossaini, H. (2022). Cyanobacteria: Model microorganisms and beyond. Microorganisms, 10(4), 696. https://doi.org/10.3390/microorganisms10040696 DOI: https://doi.org/10.3390/microorganisms10040696

Metcalf, J. S., Tischbein, M., Cox, P. A., & Stommel, E. W. (2021). Cyanotoxins and the nervous system. Toxins, 13(9), 660. https://doi.org/10.3390/toxins13090660 DOI: https://doi.org/10.3390/toxins13090660

Ndungu, L., Stubner, A., Beeman, S., Lewandowski, S., Long, L., Goguet, E., & Okech, B. (2025). Scoping review of the effects of cyanobacterial toxins on human and animal health and potential role in mosquito control. Discover Environment, 3, Article 72. https://doi.org/10.1007/s44274-025-00261-3 DOI: https://doi.org/10.1007/s44274-025-00261-3

Niedermeyer, T. H. J., Daily, A., Swiatecka-Hagenbruch, M., & Moscow, J. A. (2014). Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells. PLoS ONE, 9(3), e91476. https://doi.org/10.1371/journal.pone.0091476 DOI: https://doi.org/10.1371/journal.pone.0091476

Nykyforov, V. V., Sakun, O. A., Novokhatko, O. V., Shendryk, V. S., Meixner, K., Cherepakha, A. A., Omiotek, Z., Kalimoldayeva, S., & Nuradilova, D. (2021). The use of Microcystis aeruginosa biomass to obtain fungicidal drugs. In W. Wójcik & M. Pawłowska (Eds.), Biomass as raw material for the production of biofuels and chemicals (pp. 171–182). Routledge. https://doi.org/10.1201/9781003177593 DOI: https://doi.org/10.1201/9781003177593-16

Pandey, P., Pandey, D., Gupta, A., Gupta, R., Tiwari, S., & Singh, S. P. (2025). Cyanobacterial green chemistry: A blue-green approach for a sustainable environment, energy, and chemical production. RSC Sustainability, 3(2), 661–675. https://doi.org/10.1039/D4SU00448E DOI: https://doi.org/10.1039/D4SU00448E

Polyak, Y. M., & Sukharevich, V. I. (2025). Allelopathic properties of cyanobacteria (review). Inland Water Biology, 18(3), 565–574. https://doi.org/10.1134/S1995082925600358 DOI: https://doi.org/10.1134/S1995082925600358

Pooja, S., & Niveshika, N. (2022). Insight into the potential cyanobacterial metabolites and their screening strategies. Biosciences Biotechnology Research Asia, 19(1), 255–279. https://doi.org/10.13005/bbra/2983 DOI: https://doi.org/10.13005/bbra/2983

Rajput, S., Jain, S., Dash, D., Gupta, N., Rajpoot, R., Upadhyaya, C. P., Khan, M. L., & Koiri, R. K. (2024). Role of cyanotoxins in the development and promotion of cancer. Toxicology Reports, 13, 101798. https://doi.org/10.1016/j.toxrep.2024.101798 DOI: https://doi.org/10.1016/j.toxrep.2024.101798

Ramos, D. F., Matthiensen, A., Colvara, W., de Votto, A. P. S., Trindade, G. S., Silva, P. E. A. da, & Yunes, J. S. (2015). Antimycobacterial and cytotoxicity activity of MCs. Journal of Venomous Animals and Toxins including Tropical Diseases, 21(1), 9. https://doi.org/10.1186/s40409-015-0009-8 DOI: https://doi.org/10.1186/s40409-015-0009-8

Rastogi, R. P., & Sinha, R. P. (2009). Biotechnological and industrial significance of cyanobacterial secondary metabolites. Biotechnology Advances, 27(4), 521–539. https://doi.org/10.1016/j.biotechadv.2009.04.009Ricciardelli, A., Pollio, A., Costantini, M., & Zupo, V. (2023). Harmful and beneficial properties of cyanotoxins: Two sides of the same coin. Biotechnology Advances, 68, 108235. https://doi.org/10.1016/j.biotechadv.2023.108235 DOI: https://doi.org/10.1016/j.biotechadv.2023.108235

Rzymski, P., Poniedziałek, B., Mankiewicz-Boczek, J., Faassen, E., Jurczak, T., Gągała-Borowska, I., Ballot, A., Lürling, M., & Kokociński, M. S. (2017). Polyphasic toxicological screening of Cylindrospermopsis raciborskii and Aphanizomenon gracile isolated in Poland. Algal Research, 24(Part A), 72–80. https://doi.org/10.1016/j.algal.2017.02.011 DOI: https://doi.org/10.1016/j.algal.2017.02.011

Sainis, I., Fokas, D., Vareli, K., Tzakos, A. G., Kounnis, V., & Briasoulis, E. (2010). Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs. Marine Drugs, 8(3), 629–657. https://doi.org/10.3390/md8030629 DOI: https://doi.org/10.3390/md8030629

Sallandt, L. L., Wolf, C. A., Schuster, S., Enke, H., Enke, D., Wolber, G., & Niedermeyer, T. H. J. (2025). Derivatization of MCs can increase target inhibition while reducing cellular uptake. Journal of Natural Products, 88(1), 3–14. https://doi.org/10.1021/acs.jnatprod.4c00688 DOI: https://doi.org/10.1021/acs.jnatprod.4c00688

Sivonen, K., & Jones, G. (1999). Cyanobacterial toxins. In I. Chorus & J. Bartram (Eds.), Toxic cyanobacteria in water: A guide to public health significance, monitoring and management (pp. 41–111). E & FN Spon. https://doi.org/10.1201/9781003081449 DOI: https://doi.org/10.1201/9781003081449

Svirčev, Z., Lalić, D., Bojadžija Savić, G., Tokodi, N., Drobac Backović, D., Chen, L., Meriluoto, J., & Codd, G. A. (2019). Global geographical and historical overview of cyanotoxin distribution and cyanobacterial poisonings. Archives of Toxicology, 93(9), 2429-2481. https://doi.org/10.1007/s00204-019-02524-4 DOI: https://doi.org/10.1007/s00204-019-02524-4

Thirumurugan, D., Cholarajan, A., Raja, S. S. S., & Vijayakumar, R. (2018). An introductory chapter: Secondary metabolites. In D. Thirumurugan (Ed.), Secondary metabolites: Sources and applications. IntechOpen. https://doi.org/10.5772/intechopen.79766 DOI: https://doi.org/10.5772/intechopen.79766

Tiwari, A. K., & Tiwari, B. S. (2020). Cyanotherapeutics: An emerging field for future drug discovery. Applied Phycology, 1(1), 44–57. https://doi.org/10.1080/26388081.2020.1744480 DOI: https://doi.org/10.1080/26388081.2020.1744480

Vijayakumar, S., & Menakha, M. (2015). Pharmaceutical applications of cyanobacteria — A review. Journal of Acute Medicine, 5(1), 15-23. https://doi.org/10.1016/j.jacme.2015.02.004 DOI: https://doi.org/10.1016/j.jacme.2015.02.004

Villalobos, T., Suárez-Isla, B., & Garcia, C. (2025). Health and environmental impacts of cyanobacteria and cyanotoxins from freshwater to seawater. Toxins, 17(3), 126. https://doi.org/10.3390/toxins17030126 DOI: https://doi.org/10.3390/toxins17030126

Wan, N.-F., Fu, L., Dainese, M., Kiær, L. P., Hu, Y.-Q., Xin, F., Goulson, D., Woodcock, B. A., Vanbergen, A. J., Spurgeon, D. J., Shen, S., & Scherber, C. (2025). Pesticides have negative effects on non-target organisms. Nature Communications, 16, 1360. https://doi.org/10.1038/s41467-025-56732-x DOI: https://doi.org/10.1038/s41467-025-56732-x

Wang, R., Tai, Y., Wan, X., Ruan, W., Man, Y., Wang, J., Yang, Y., & Yang, Y. (2018). Enhanced removal of Microcystis bloom and microcystin-LR using microcosm constructed wetlands with bioaugmentation of degrading bacteria. Chemosphere, 210, 29–37. https://doi.org/10.1016/j.chemosphere.2018.06.140 DOI: https://doi.org/10.1016/j.chemosphere.2018.06.140

Weiss, M. B., Borges, R. M., Sullivan, P., Domingues, J. P. B., da Silva, F. H. S., Trindade, V. G. S., Luo, S., Orjala, J., & Crnkovic, C. M. (2025). Chemical diversity of cyanobacterial natural products. Natural Product Reports, 42, 6–49. https://doi.org/10.1039/D4NP00040D DOI: https://doi.org/10.1039/D4NP00040D

Yang, J., Deng, X., Xian, Q., Qian, X., & Li, A. (2014). Allelopathic effect of Microcystis aeruginosa on Microcystis wesenbergii: Microcystin-LR as a potential allelochemical. Hydrobiologia, 727, 65–73. https://doi.org/10.1007/s10750-013-1787-z DOI: https://doi.org/10.1007/s10750-013-1787-z

Żak, A., & Kosakowska, A. (2016). Cyanobacterial and microalgal bioactive compounds – The role of secondary metabolites in allelopathic interactions. Oceanological and Hydrobiological Studies, 45(1), 131–143. https://doi.org/10.1515/ohs-2016-0013 DOI: https://doi.org/10.1515/ohs-2016-0013

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11.01.2026

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Sever Kaya, D. (2026). The paradox of cyanotoxins: from natural toxins to biotechnological resources. EUCHEMBIOJ Reviews, 2(1), e26003. https://doi.org/10.62063/rev-32

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