Article abstract
Nature Chemical Biology 5, 494 - 501 (2009)
Published online: 17 May 2009 | doi:10.1038/nchembio.176
Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting
Katja M Fisch1,5, Cristian Gurgui1,5, Nina Heycke1, Sonia A van der Sar1, Sally A Anderson2, Victoria L Webb2, Stefan Taudien3, Matthias Platzer3, Brent K Rubio4, Sarah J Robinson4, Phillip Crews4 & Jörn Piel1
Abstract
There is increasing evidence that uncultivated bacterial symbionts are the true producers of numerous bioactive compounds isolated from marine sponges. The localization and heterologous expression of biosynthetic genes could clarify this issue and provide sustainable supplies for a wide range of pharmaceuticals. However, identification of genes in the usually highly complex symbiont communities remains a challenging task. For polyketides, one of the most important groups of sponge-derived drug candidates, we have developed a general strategy that allows one to rapidly access biosynthetic gene clusters based on chemical moieties. Using this method, we targeted polyketide synthase genes from two different sponge metagenomes. We have obtained from a sponge-bacterial association a complete pathway for the rare and potent antitumor agent psymberin from Psammocinia aff. bulbosa. The data support the symbiont hypothesis and provide insights into natural product evolution in previously inaccessible bacteria.
- Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany.
- National Institute of Water & Atmospheric Research Ltd., Wellington, New Zealand.
- Genome Analysis, Leibniz-Institute for Age Research–Fritz Lipmann Institute, Jena, Germany.
- Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California, USA.
- These authors contributed equally to this work.
Correspondence to: Jörn Piel1 e-mail: joern.piel@uni-bonn.de
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