Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis

Yi Qiang Cheng, Gong Li Tang, Ben Shen

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

Type I polyketide synthases (PKSs) are multifunctional enzymes that are organized into modules, each of which minimally contains a β-ketoacyl synthase, an acyltransferase (AT), and an acyl carrier protein. Here we report that the leinamycin (LNM) biosynthetic gene cluster from Streptomyces atroolivaceus S-140 consists of two PKS genes, Inml and InmJ, that encode six PKS modules, none of which contain the cognate AT domain. The only AT activity identified within the Inm gene cluster is a discrete AT protein encoded by InmG. Inactivation of InmG, Inml, or InmJ in vivo abolished LNM biosynthesis. Biochemical characterization of LnmG in vitro showed that it efficiently and specifically loaded malonyl CoA to all six PKS modules. These findings unveiled a previously unknown PKS architecture that is characterized by a discrete, iteratively acting AT protein that loads the extender units in trans to "AT-less" multifunctional type I PKS proteins for polyketide biosynthesis. This PKS structure provides opportunities for PKS engineering as exemplified by overexpressing InmG to improve LNM production.

Original languageEnglish
Pages (from-to)3149-3154
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
DOIs
StatePublished - 18 Mar 2003

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