Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge <i>Theonella swinhoei</i>
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- Jörn Piel
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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- Dequan Hui
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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- Gaiping Wen
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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- Daniel Butzke
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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- Matthias Platzer
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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- Nobuhiro Fusetani
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
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- Shigeki Matsunaga
- Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
説明
<jats:p> Bacterial symbionts have long been suspected to be the true producers of many drug candidates isolated from marine invertebrates. Sponges, the most important marine source of biologically active natural products, have been frequently hypothesized to contain compounds of bacterial origin. This symbiont hypothesis, however, remained unproven because of a general inability to cultivate the suspected producers. However, we have recently identified an uncultured <jats:italic>Pseudomonas</jats:italic> sp. symbiont as the most likely producer of the defensive antitumor polyketide pederin in <jats:italic>Paederus fuscipes</jats:italic> beetles by cloning the putative biosynthesis genes. Here we report closely related genes isolated from the highly complex metagenome of the marine sponge <jats:italic>Theonella swinhoei</jats:italic> , which is the source of the onnamides and theopederins, a group of polyketides that structurally resemble pederin. Sequence features of the isolated genes clearly indicate that it belongs to a prokaryotic genome and should be responsible for the biosynthesis of almost the entire portion of the polyketide structure that is correlated with antitumor activity. Besides providing further proof for the role of the related beetle symbiont-derived genes, these findings raise intriguing ecological and evolutionary questions and have important general implications for the sustainable production of otherwise inaccessible marine drugs by using biotechnological strategies. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 101 (46), 16222-16227, 2004-11
Proceedings of the National Academy of Sciences
