双功能酰基转移酶/脱羧酶LnmK是聚酮生物合成中β-烷基化缺失的环节。
Bifunctional acyltransferase/decarboxylase LnmK as the missing link for beta-alkylation in polyketide biosynthesis.
作者信息
Liu Tao, Huang Yong, Shen Ben
机构信息
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705-2222, USA.
出版信息
J Am Chem Soc. 2009 May 27;131(20):6900-1. doi: 10.1021/ja9012134.
Abstract
Beta-alkylations contribute to the vast structural diversity displayed by polyketide natural products. A unified pathway has been proposed for introduction of both beta-methyl and beta-ethyl branches catalyzed by hydroxymethylglutaryl-CoA synthase homologues that utilize acetyl- or propionyl-S-acyl carrier protein (ACP) as a substrate. While the origin of acetyl-S-ACP has been established, that of propionyl-S-ACP remains unknown. Here we report the characterization of LnmK from the leinamycin biosynthetic machinery as a bifunctional acyltransferase/decarboxylase (AT/DC) that derives propionyl-S-ACP from methylmalonyl-CoA, accounting for the missing link of the beta-ethyl or propionyl branch in polyketide biosynthesis. LnmK represents an emerging family of novel AT/DC enzymes and could be exploited by combinatorial biosynthesis methods to engineer novel polyketides, especially those with beta-alkyl branches.
摘要
β-烷基化作用促成了聚酮类天然产物所展现出的巨大结构多样性。已提出一条统一途径，用于由羟甲基戊二酰辅酶A合酶同系物催化引入β-甲基和β-乙基支链，这些同系物利用乙酰基或丙酰基-S-酰基载体蛋白（ACP）作为底物。虽然乙酰基-S-ACP的来源已明确，但丙酰基-S-ACP的来源仍不清楚。在此，我们报道了来自链黑霉素生物合成机制的LnmK的特性，它是一种双功能酰基转移酶/脱羧酶（AT/DC），可从甲基丙二酰辅酶A衍生出丙酰基-S-ACP，解释了聚酮生物合成中β-乙基或丙酰基支链缺失的环节。LnmK代表了一个新兴的新型AT/DC酶家族，可通过组合生物合成方法加以利用，以设计新型聚酮类化合物，特别是那些带有β-烷基支链的化合物。
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