de Villiers Marianne, Puthan Veetil Vinod, Raj Hans, de Villiers Jandré, Poelarends Gerrit J
Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
ACS Chem Biol. 2012 Oct 19;7(10):1618-28. doi: 10.1021/cb3002792. Epub 2012 Aug 16.
Ammonia lyases catalyze the formation of α,β-unsaturated bonds by the elimination of ammonia from their substrates. This conceptually straightforward reaction has been the emphasis of many studies, with the main focus on the catalytic mechanism of these enzymes and/or the use of these enzymes as catalysts for the synthesis of enantiomerically pure α-amino acids. In this Review aspartate ammonia lyase and 3-methylaspartate ammonia lyase, which represent two different enzyme superfamilies, are discussed in detail. In the past few years, the three-dimensional structures of these lyases in complex with their natural substrates have revealed the details of two elegant catalytic strategies. These strategies exploit similar deamination mechanisms that involve general-base catalyzed formation of an enzyme-stabilized enolate anion (aci-carboxylate) intermediate. Recent progress in the engineering and application of these enzymes to prepare enantiopure l-aspartic acid derivatives, which are highly valuable as tools for biological research and as chiral building blocks for pharmaceuticals and food additives, is also discussed.
氨裂解酶通过从其底物中消除氨来催化形成α,β-不饱和键。这个概念上简单直接的反应一直是许多研究的重点，主要集中在这些酶的催化机制和/或将这些酶用作合成对映体纯α-氨基酸的催化剂。在本综述中，详细讨论了代表两个不同酶超家族的天冬氨酸氨裂解酶和3-甲基天冬氨酸氨裂解酶。在过去几年中，这些裂解酶与其天然底物复合物的三维结构揭示了两种精妙催化策略的细节。这些策略利用了类似的脱氨机制，涉及一般碱催化形成酶稳定的烯醇负离子（酸式羧酸盐）中间体。还讨论了这些酶在制备对映体纯L-天冬氨酸衍生物方面的工程和应用的最新进展，这些衍生物作为生物学研究工具以及药物和食品添加剂的手性构建块具有很高的价值。
