The swinholide biosynthetic gene cluster from a terrestrial cyanobacterium Nostoc sp. UHCC 0450
Humisto, A., Jokela, J., Liu, L., Wahlsten, M., Wang, H., Permi, P., Machado, J. P., Antunes, A., Fewer, D. P., & Sivonen, K. (2018). The swinholide biosynthetic gene cluster from a terrestrial cyanobacterium Nostoc sp. UHCC 0450. Applied and Environmental Microbiology, 84(3), e02321-17. https://doi.org/10.1128/AEM.02321-17
Published inApplied and Environmental Microbiology
© 2018 Humisto et al. This is an open access article distributed under the terms of the Creative Commons License.
Swinholides are 42-carbon ring polyketides with a 2-fold axis of symmetry. They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge Theonella sp. and were long suspected to be produced by symbiotic bacteria. Misakinolide, a structural variant of swinholide, was recently demonstrated to be the product of a symbiotic heterotrophic proteobacterium. Here, we report the production of swinholide A by an axenic strain of the terrestrial cyanobacterium Nostoc sp. strain UHCC 0450. We located the 85-kb trans-AT polyketide synthase (PKS) swinholide biosynthesis gene cluster from a draft genome of Nostoc sp. UHCC 0450. The swinholide and misakinolide biosynthesis gene clusters share an almost identical order of catalytic domains, with 85% nucleotide sequence identity, and they group together in phylogenetic analysis. Our results resolve speculation around the true producer of swinholides and demonstrate that bacteria belonging to two distantly related phyla both produce structural variants of the same natural product. In addition, we described a biosynthesis cluster from Anabaena sp. strain UHCC 0451 for the synthesis of the cytotoxic and antifungal scytophycin. All of these biosynthesis gene clusters were closely related to each other and created a group of cytotoxic macrolide compounds produced by trans-AT PKSs of cyanobacteria and proteobacteria. IMPORTANCE Many of the drugs in use today originate from natural products. New candidate compounds for drug development are needed due to increased drug resistance. An increased knowledge of the biosynthesis of bioactive compounds can be used to aid chemical synthesis to produce novel drugs. Here, we show that a terrestrial axenic culture of Nostoc cyanobacterium produces swinholides, which have been previously found only from marine sponge or samples related to them. Swinholides are polyketides with a 2-fold axis of symmetry, and they are potent cytotoxins that disrupt the actin cytoskeleton. We describe the biosynthesis gene clusters of swinholide from Nostoc cyanobacteria, as well as the related cytotoxic and antifungal scytophycin from Anabaena cyanobacteria, and we study the evolution of their trans-AT polyketide synthases. Interestingly, swinholide is closely related to misakinolide produced by a symbiotic heterotrophic proteobacterium, demonstrating that bacteria belonging to two distantly related phyla and different habitats can produce similar natural products. ...
PublisherAmerican Society for Microbiology
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Related funder(s)Academy of Finland
Funding program(s)Academy Project, AoF
Additional information about fundingThis work was supported by the Academy of Finland grants 258827 and 273798 to K.S. and 288235 to P.P. A.H. is a student at the Doctoral Programme in Microbiology and Biotechnology. A.A. was funded in part by the Strategic Funding grant UID/Multi/04423/2013 through national funds provided by the Portuguese National Science Foundation (FCT) and the European Regional Development Fund (ERDF) in the framework of the program PT2020, by the European Structural and Investment Funds (ESIF) through the Competitiveness and Internationalization Operational Program—COMPETE 2020, and by the Structured Programs of R&D&I INNOVMAR (NORTE-01-0145-FEDER-000035—NOVELMAR), CORAL NORTE (NORTE-01-0145-FEDER-000036), and MarInfo (NORTE-01-0145-FEDER-000031), funded by the Northern Regional Operational Program (NORTE2020) through the ERDF. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. ...
Except where otherwise noted, this item's license is described as © 2018 Humisto et al. This is an open access article distributed under the terms of the Creative Commons License.
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