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They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge\n            <jats:italic>Theonella<\/jats:italic>\n            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\n            <jats:named-content content-type=\"genus-species\">Nostoc<\/jats:named-content>\n            sp. strain UHCC 0450. We located the 85-kb\n            <jats:italic>trans<\/jats:italic>\n            -AT polyketide synthase (PKS) swinholide biosynthesis gene cluster from a draft genome of\n            <jats:named-content content-type=\"genus-species\">Nostoc<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">Anabaena<\/jats:named-content>\n            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\n            <jats:italic>trans<\/jats:italic>\n            -AT PKSs of cyanobacteria and proteobacteria.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            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\n            <jats:named-content content-type=\"genus-species\">Nostoc<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">Nostoc<\/jats:named-content>\n            cyanobacteria, as well as the related cytotoxic and antifungal scytophycin from\n            <jats:named-content content-type=\"genus-species\">Anabaena<\/jats:named-content>\n            cyanobacteria, and we study the evolution of their\n            <jats:italic>trans<\/jats:italic>\n            -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.\n          <\/jats:p>","DOI":"10.1128\/aem.02321-17","type":"journal-article","created":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T16:20:24Z","timestamp":1510935624000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["The Swinholide Biosynthesis Gene Cluster from a Terrestrial Cyanobacterium, Nostoc sp. Strain UHCC 0450"],"prefix":"10.1128","volume":"84","author":[{"given":"Anu","family":"Humisto","sequence":"first","affiliation":[{"name":"Department of Food and Environmental Sciences, Viikki Biocenter 1, University of Helsinki, Helsinki, Finland"}]},{"given":"Jouni","family":"Jokela","sequence":"additional","affiliation":[{"name":"Department of Food and Environmental Sciences, Viikki Biocenter 1, University of Helsinki, Helsinki, Finland"}]},{"given":"Liwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Food and Environmental Sciences, Viikki Biocenter 1, University of Helsinki, Helsinki, Finland"}]},{"given":"Matti","family":"Wahlsten","sequence":"additional","affiliation":[{"name":"Department of Food and Environmental Sciences, Viikki Biocenter 1, University of Helsinki, Helsinki, Finland"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Food and Environmental Sciences, Viikki Biocenter 1, University of Helsinki, Helsinki, Finland"}]},{"given":"Perttu","family":"Permi","sequence":"additional","affiliation":[{"name":"Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Helsinki, Finland"},{"name":"Department of Biological and Environmental Science, Nanoscience Center, University of Jyv\u00e4skyl\u00e4, Jyv\u00e4skyl\u00e4, Finland"},{"name":"Department of Chemistry, Nanoscience Center, University of Jyv\u00e4skyl\u00e4, Jyv\u00e4skyl\u00e4, Finland"}]},{"given":"Jo\u00e3o Paulo","family":"Machado","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Porto, Portugal"}]},{"given":"Agostinho","family":"Antunes","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Porto, Portugal"},{"name":"Department of Biology, Faculty of Sciences, University of Porto, Porto, 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