Context-dependent behavior of the enterocin iterative polyketide synthase: A new model for ketoreduction

被引：48
作者：
Hertweck, C
Xiang, LK
Kalaitzis, JA
Cheng, Q
Palzer, M
Moore, BS [1 ]
机构：
[1] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
[2] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA
[3] Hans Knoll Inst Nat Prod Res, D-07745 Jena, Germany
来源：
CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 04期
关键词：
D O I：
10.1016/j.chembiol.2004.03.018
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：461 / 468
页数：8
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