Department of Chemistry, Christopher Ingold Laboratories, University College London, UK.
FEBS J. 2013 Dec;280(24):6374-94. doi: 10.1111/febs.12496. Epub 2013 Sep 13.
Thiamine diphosphate-dependent enzymes are broadly distributed in all organisms, and they catalyse a broad range of C-C bond forming and breaking reactions. Enzymes belonging to the structural families of decarboxylases and transketolases have been particularly well investigated concerning their substrate range, mechanism of stereoselective carboligation and carbolyase reaction. Both structurally different enzyme families differ also in stereoselectivity: enzymes from the decarboxylase family are predominantly R-selective, whereas those from the transketolase family are S-selective. In recent years a key focus of our studies has been on stereoselective benzoin condensation-like 1,2-additions. Meanwhile, several S-selective variants of pyruvate decarboxylase, benzoylformate decarboxylase and 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC) synthase as well as R-selective transketolase variants were created that allow access to a broad range of enantiocomplementary α-hydroxyketones and α,α'-dihydroxyketones. This review covers recent studies and the mechanistic understanding of stereoselective C-C bond forming thiamine diphosphate-dependent enzymes, which has been guided by structure-function analyses based on mutagenesis studies and from influences of different substrates and organic co-solvents on stereoselectivity.
依赖硫胺素二磷酸的酶广泛分布于所有生物体中，它们催化广泛的 C-C 键形成和断裂反应。属于脱羧酶和转酮醇酶结构家族的酶在其底物范围、立体选择性卡罗利加和卡罗利酶反应的机制方面已经得到了特别深入的研究。这两个结构不同的酶家族在立体选择性上也有所不同：脱羧酶家族的酶主要是 R 选择性的，而转酮醇酶家族的酶是 S 选择性的。近年来，我们研究的重点一直是立体选择性安息香缩合样 1,2-加成。同时，还创建了几种 S 选择性的丙酮酸脱羧酶、苯甲酰甲酸脱羧酶和 2-琥珀酰-5-烯醇丙酮酸-6-羟基-3-环己烯-1-羧酸酯（SEPHCHC）合酶以及 R 选择性转酮醇酶变体，这些变体可用于制备广泛的对映体互补的α-羟基酮和α,α'-二羟基酮。这篇综述涵盖了最近的研究以及对依赖硫胺素二磷酸的立体选择性 C-C 键形成酶的机制理解，这些研究受到基于诱变研究的结构-功能分析以及不同底物和有机溶剂对立体选择性的影响的指导。
