Evolution of non-linear polyketide biosynthesis in the aureothin and neoaureothin pathways
CHRISTIAN HERTWECK
Leibniz-Institut für
Naturstoff-Forschung und Infektionsbiologie
Hans-Knöll-Institut und Lehrstuhl für Biomolekulare Chemie
Beutenbergstraße 11a
D-07745 Jena
christian.hertweck@hki-jena.de
www.hki-jena.de
Aureothin and neoaureothin represent rare nitroaryl pyrone compounds from Streptomycetes, which are assembled by non-collinear type I polyketide synthases (PKS). Cloning, sequencing and functional studies of the aureothin and neoaureothin biosynthesis gene clusters provide new and unexpected insights into the formation of the closely related metabolites. In both pathways, type I polyketide synthases lacking designated loading domains are loaded with a novel p-nitro benzoate starter unit. Most remarkably, the subsequent assembly of the aureothin and neoaureothin polyketide backbones (five vs. seven Claisen condensations) breaches with the principle of co-linearity, as individual modules of the type I polyketide synthases are used iteratively. In order to elucidate the evolutionary relationship between both systems a series of mutagenesis, rational engineering and cross-complementation experiments as well as feeding experiments and phylogenetic studies were performed.
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