C-O bond formation by polyketide synthases |
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| Authors: | Kwon Hyung-Jin Smith Wyatt C Scharon A Janelle Hwang Sung Hee Kurth Mark J Shen Ben |
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| Affiliation: | Division of Pharmaceutical Sciences and, Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA. |
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| Abstract: | Polyketide synthases (PKSs) assemble the polyketide carbon backbone by sequential decarboxylative condensation of acyl coenzyme A (CoA) precursors, and the C-C bond-forming step in this process is catalyzed by the beta-ketoacyl synthase (KS) domain or subunit. Genetic and biochemical characterization of the nonactin biosynthesis gene cluster from Streptomyces griseus revealed two KSs, NonJ and NonK, that are highly homologous to known KSs but catalyze sequential condensation of the acyl CoA substrates by forming C-O rather than C-C bonds. This chemistry can be used in PKS engineering to increase the scope and diversity of polyketide biosynthesis. |
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