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C-O bond formation by polyketide synthases.

Hyung-Jin Kwon·Wyatt C Smith·A Janelle Scharon·Sung Hee Hwang·Mark J Kurth·Ben Shen
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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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3-Oxoacyl-(Acyl-Carrier-Protein) SynthaseAcyl Coenzyme AAmino Acid SequenceBinding SitesCatalysisChromatography, High Pressure LiquidGenes, BacterialMacrolidesMolecular Sequence DataMultienzyme ComplexesMultigene FamilyMutationProtein EngineeringProtein SubunitsSequence AlignmentSpectrometry, Mass, Electrospray IonizationStreptomycesStreptomyces griseusTransformation, BacterialJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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Hyung-Jin Kwon, Wyatt C Smith, A Janelle Scharon, Sung Hee Hwang, Mark J Kurth, Ben Shen. 2002-08-23. C-O bond formation by polyketide synthases.. https://doi.org/10.1126/science.1073175

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