Context-dependent behavior of the enterocin iterative polyketide synthase

a new model for ketoreduction

Christian Hertweck, Longkuan Xiang, John A. Kalaitzis, Qian Cheng, Michelle Palzer, Bradley S. Moore*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Heterologous expression and mutagenesis of the enterocin type II polyketide synthase (PKS) system suggest for the first time that the association of an extended set of proteins and substrates is needed for the effective production of the enterocin-wailupemycin polyketides. In the absence of its endogenous ketoreductase (KR) EncD in either the enterocin producer "Streptomyces maritimus" or the engineered host S. lividans K4-114, the enterocin minimal PKS is unable to produce benzoate-primed polyketides, even when complemented with the homologous actinorhodin KR ActIII or with EncD active site mutants. These data suggest that the enterocin PKS requires EncD to serve a catalytic and not just a structural role in the functional PKS enzyme complex. This strongly implies that EncD reduces the polyketide chain during elongation rather than after its complete assembly, as suggested for most type II PKSs.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalChemistry and Biology
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

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