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Science 23 August 2002:
Vol. 297. no. 5585, pp. 1327 - 1330
DOI: 10.1126/science.1073175
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Reports

C-O Bond Formation by Polyketide Synthases

Hyung-Jin Kwon,1 Wyatt C. Smith,2 A. Janelle Scharon,1 Sung Hee Hwang,2 Mark J. Kurth,2 Ben Shen123*

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.

1 Division of Pharmaceutical Sciences and
3 Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA.
2 Department of Chemistry, University of California, Davis, CA 95616, USA.
*   To whom correspondence should be addressed. E-mail: bshen{at}pharmacy.wisc.edu

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