期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 28, 期 6, 页码 1071-1076出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2018.02.019
关键词
Carbocyclic nucleosides; 2-azabicyclo[2.2.1] hept-5-en-3-one; (+)-gamma-Lactamase; Nitrile hydratase; Enzymatic resolution
资金
- National Natural Science Foundation of China - China (NSFC) [21706005]
- China Postdoctoral Science Foundation - China [2017 M610747]
- Fundamental Research Funds for the Central Universities [ZY1713]
- National Great Science and Technology Projects [2018ZX09721001]
Based on bioinformatics analysis, the promiscuous (+)-gamma-lactamase activity of an amidase was identified in Rhodococcus erythropolis PR4 and found to be involved in the nitrile hydratase pathway. The amidase is highly enantioselective and can be used in the kinetic resolution of the Vince lactam. The known structure provides a rare insight into the catalytic mechanism of (+)-gamma-lactamase with absolute chiral selectivity. This lactamase was cloned, purified, biochemically characterized, and demonstrated to be an ideal catalyst for the preparation of carbocyclic nucleosides of pharmaceutical interest. The chiral selectivity of this enzyme was investigated by molecular docking and site-specific mutagenesis, which provides a foundation for further engineering of these versatile biocatalysts. (C) 2018 Published by Elsevier Ltd.
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