State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China.
J Ind Microbiol Biotechnol. 2018 Dec;45(12):1017-1031. doi: 10.1007/s10295-018-2093-6. Epub 2018 Oct 23.
γ-Lactamases are versatile enzymes used for enzymatic kinetic resolution of racemic Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) in the industry. Optically pure enantiomers and their hydrolytic products are widely employed as key chemical intermediates for developing a wide range of carbocyclic nucleoside medicines, including US FDA-approved drugs peramivir and abacavir. Owing to the broad applications in the healthcare industry, the resolution process of Vince lactam has witnessed tremendous progress during the past decades. Some of the most important advances are the enzymatic strategies involving γ-lactamases. The strong industrial demand drives the progress in various strategies for discovering novel biocatalysts. In the past few years, several new scientific breakthroughs, including the genome-mining strategy and elucidation of several crystal structures, boosted the research on γ-lactamases. So far, several families of γ-lactamases for resolution of Vince lactam have been discovered, and their number is continuously increasing. The purpose of this mini-review is to describe the discovery strategy and classification of these intriguing enzymes and to cover our current knowledge on their potential biological functions. Moreover, structural properties are described in addition to their possible catalytic mechanisms. Additionally, recent advances in the newest approaches, such as immobilization to increase stability, and other engineering efforts are introduced.
γ-内酰胺酶是一种多功能酶,用于工业上对消旋 Vince 内酰胺(2-氮杂双环[2.2.1]庚-5-烯-3-酮)进行酶促动力学拆分。光学纯对映异构体及其水解产物广泛用作开发各种碳环核苷药物的关键化学中间体,包括美国食品和药物管理局批准的药物帕拉米韦和阿巴卡韦。由于在医疗保健行业的广泛应用,Vince 内酰胺的拆分过程在过去几十年中取得了巨大的进展。其中一些最重要的进展是涉及γ-内酰胺酶的酶促策略。强烈的工业需求推动了发现新型生物催化剂的各种策略的进步。在过去的几年中,包括基因组挖掘策略和几个晶体结构的阐明在内的几项新的科学突破,推动了γ-内酰胺酶的研究。到目前为止,已经发现了用于拆分 Vince 内酰胺的几类γ-内酰胺酶,并且它们的数量还在不断增加。本文的目的是描述这些有趣的酶的发现策略和分类,并涵盖我们目前对它们潜在生物学功能的了解。此外,还描述了结构特性及其可能的催化机制。此外,还介绍了最近在最新方法(例如固定化以提高稳定性)和其他工程努力方面的进展。