title: Context-dependent behavior of the enterocin iterative polyketide synthase; a new model for ketoreduction.
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.
authors.affiliation: Hans-Knöll-Institute for Natural Products Research, Beutenbergstrasse 11a, 07745 Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.forename: Longkuan
authors.initials: L
authors.lastname: Xiang
authors.forename: John A
authors.initials: JA
authors.lastname: Kalaitzis
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.forename: Michelle
authors.initials: M
authors.lastname: Palzer
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000737:chemistry* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D010084:Oxidation-Reduction; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001952:Bridged-Ring Compounds; C012306:enterocin; D000429:Alcohol Oxidoreductases