聚酮化合物生物合成中立体化学控制的生化基础。
The biochemical basis for stereochemical control in polyketide biosynthesis.
机构信息
Department of Chemistry, Box H, Brown University, Providence, Rhode Island 02912-9108, USA.
出版信息
J Am Chem Soc. 2009 Dec 30;131(51):18501-11. doi: 10.1021/ja908296m.
Abstract
One of the most striking features of complex polyketides is the presence of numerous methyl- and hydroxyl-bearing stereogenic centers. To investigate the biochemical basis for the control of polyketide stereochemistry and to establish the timing and mechanism of the epimerization at methyl-bearing centers, a series of incubations was carried out using reconstituted components from a variety of modular polyketide synthases. In all cases the stereochemistry of the product was directly correlated with the intrinsic stereospecificity of the ketoreductase domain, independent of the particular chain elongation domains that were used, thereby establishing that methyl group epimerization, when it does occur, takes place after ketosynthase-catalyzed chain elongation. The finding that there were only minor differences in the rates of product formation observed for parallel incubations using an epimerizing ketoreductase domain and the nonepimerizing ketoreductase domain supports the proposal that the epimerization is catalyzed by the ketoreductase domain itself.
摘要
复杂聚酮类化合物最显著的特征之一是存在许多带有甲基和羟基的手性中心。为了研究聚酮立体化学控制的生化基础，并确定带有甲基中心的差向异构化的时间和机制，使用来自各种模块化聚酮合酶的重组成分进行了一系列孵育。在所有情况下，产物的立体化学都与酮还原酶结构域的固有立体特异性直接相关，而与使用的特定链伸长结构域无关，从而确定当差向异构化发生时，它发生在酮合酶催化的链伸长之后。使用差向异构化酮还原酶结构域和非差向异构化酮还原酶结构域进行平行孵育时观察到的产物形成速率只有很小差异的发现支持这样的假设，即差向异构化是由酮还原酶结构域本身催化的。
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