12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Swinholide Biosynthesis Gene Cluster from a Terrestrial Cyanobacterium, Nostoc sp. Strain UHCC 0450

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          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.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: not found
          • Article: not found

          Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found
            Is Open Access

            An environmental bacterial taxon with a large and distinct metabolic repertoire.

            Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such 'talented' producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus 'Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. 'Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum 'Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of 'Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              PHYLIP—phylogeny inference package (version 2)

                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                Appl Environ Microbiol
                Appl. Environ. Microbiol
                aem
                aem
                AEM
                Applied and Environmental Microbiology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0099-2240
                1098-5336
                17 November 2017
                17 January 2018
                1 February 2018
                17 January 2018
                : 84
                : 3
                : e02321-17
                Affiliations
                [a ]Department of Food and Environmental Sciences, Viikki Biocenter 1, University of Helsinki, Helsinki, Finland
                [b ]Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
                [c ]Department of Biological and Environmental Science, Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland
                [d ]Department of Chemistry, Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland
                [e ]CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Porto, Portugal
                [f ]Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal
                University of Bayreuth
                Author notes
                Address correspondence to Kaarina Sivonen, kaarina.sivonen@ 123456helsinki.fi .

                Citation Humisto A, Jokela J, Liu L, Wahlsten M, Wang H, Permi P, Machado JP, Antunes A, Fewer DP, Sivonen K. 2018. The swinholide biosynthesis gene cluster from a terrestrial cyanobacterium, Nostoc sp. strain UHCC 0450. Appl Environ Microbiol 84:e02321-17. https://doi.org/10.1128/AEM.02321-17.

                Article
                02321-17
                10.1128/AEM.02321-17
                5772238
                29150506
                189e7193-349c-4dcf-9de6-a86f807e8007
                Copyright © 2018 Humisto et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 23 October 2017
                : 3 November 2017
                Page count
                supplementary-material: 1, Figures: 7, Tables: 1, Equations: 0, References: 54, Pages: 14, Words: 8419
                Funding
                Funded by: National Science Foundation Portugal;
                Award ID: UID/Multi/04423/2013
                Award Recipient :
                Funded by: European Structural and Investment Funds;
                Award ID: NORTE-01-0145-FEDER-000035 - NOVELMAR NORTE-01-0145-FEDER-000036 NORTE-01-0145-FEDER-000031
                Award Recipient :
                Funded by: The Academy of Finland;
                Award ID: 258827
                Award Recipient :
                Funded by: The Academy of Finland;
                Award ID: 273798
                Award Recipient :
                Funded by: The Academy of Finland;
                Award ID: 288235
                Award Recipient :
                Funded by: EC | European Regional Development Fund (ERDF), https://doi.org/10.13039/501100008530;
                Award ID: PT2020
                Award Recipient :
                Categories
                Environmental Microbiology
                Spotlight
                Custom metadata
                February 2018

                Microbiology & Virology
                cyanobacteria,nostoc,“candidatus entotheonella”,polyketides,trans-at pks,swinholide,scytophycin,horizontal gene transfer,anabaena

                Comments

                Comment on this article