Abstract
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.
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This work was supported by the National Natural Science Foundation of China (NSFC, Grant No. 21706005), China Postdoctoral Science Foundation (Grant No. 2017M610747), the Fundamental Research Funds for the Central Universities (No. XK1802-8), and National Great Science and Technology Projects (2018ZX09721001).
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Zhu, S., Zheng, G. Dynamic kinetic resolution of Vince lactam catalyzed by γ-lactamases: a mini-review. J Ind Microbiol Biotechnol 45, 1017–1031 (2018). https://doi.org/10.1007/s10295-018-2093-6
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DOI: https://doi.org/10.1007/s10295-018-2093-6