Tuesday, August 12, 2008 - 4:00 PM

Cryptic PKS-NRPS Pathways in Bacteria and Fungi

Christian Hertweck, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr. 11a, Jena, 07745, Germany

Many therapeutically important natural products are synthesized produced by thiotemplate assembly lines such as polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS) or hybrids thereof (PKS/NRPS). In the post-genomic era it has become increasingly apparent that the vast number of predicted PKS / NRPS biosynthesis genes of microorganisms is not reflected by the metabolic profile observed under standard fermentation conditions. Many compounds are simply overlooked, and in the absence of a particular, in most cases unknown trigger gene loci may remain silent. A few examples are given to illustrate how new biologically active compounds can be discovered by genomic information, molecular methods and chemical analyses. In addition, a particularly rare example of a cryptic biosynthetic pathway in a fungus is presented: the antimitotic agent rhizoxin is not produced by the fungus but by bacteria residing within the cytosol.

References

S. Bergmann, J. Schümann, K. Scherlach, C. Lange, A.A. Brakhage & C. Hertweck, Genomics-Driven Discovery of PKS-NRPS Hybrid Metabolites from Aspergillus nidulans, Nature Chem. Biol. 2007, 3, 213-217.

T. Nguyen, K. Ishida, H. Jenke-Kodama, E. Dittmann, C. Gurgui, T. Hochmuth, S. Taudien, M. Platzer, C. Hertweck & J. Piel, Mosaic Structure of trans-AT Polyketide Synthases Reveals New Strategies for Natural Product Discovery and Pathway Dissection, Nature Biotechnol. 2008, 2008, 26, 225-233.

L.P. Partida-Martinez & C. Hertweck, Pathogenic Fungus Harbours Endosymbiotic Bacteria for Toxin Production, Nature 2005, 437, 884-888.


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