Context-dependent behavior of the enterocin iterative polyketide synthase; a new model for ketoreduction.
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.
Hertweck
Christian
C
Hans-Knöll-Institute for Natural Products Research, Beutenbergstrasse 11a, 07745 Jena, Germany.
Xiang
Longkuan
L
Kalaitzis
John A
JA
Cheng
Qian
Q
Palzer
Michelle
M
Moore
Bradley S
BS
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
D001426:Bacterial Proteins; D001952:Bridged-Ring Compounds; C012306:enterocin; D000429:Alcohol Oxidoreductases