title: Efficient synthesis of the intermediate of abacavir and carbovir using a novel (+)-γ-lactamase as a catalyst.
abstract: The enantiomers of 2-azabicyclo[2.2.1]hept-5-en-3-one (γ-lactam) are key chiral synthons in the synthesis of antiviral drugs such as carbovir and abacavir. (+)-γ-Lactamase can be used as a catalyst in the enzymatic preparation of optically pure (-)-γ-lactam. Here, a (+)-γ-lactamase discovered from Bradyrhizobium japonicum USDA 6 by sequence-structure guided genome mining was cloned, purified and characterized. The enzyme possesses a significant catalytic activity towards γ-lactam. The active site of the (+)-γ-lactamase was studied by homologous modeling and molecular docking, and the accuracy of the prediction was confirmed by site-specific mutagenesis. The (+)-γ-lactamase reveals the great practical potential as an enzymatic method for the efficient production of carbocyclic nucleosides of pharmaceutical interest.
authors.affiliation: State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
authors.forename: Shuaihua
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Chemistry, Biochemistry, Philipps-University Marburg, Hans-Meerwein-Strasse 4 and LOEWE-Centre for Synthetic Microbiology, D-35032 Marburg, Germany.
authors.forename: Shaozhou
authors.initials: S
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
authors.forename: Yingxiu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China. Electronic address: zhenggj@mail.buct.edu.cn.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D015224:Dideoxynucleosides / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D000099227:Abacavir
chemical_list: D000581:Amidohydrolases; D015224:Dideoxynucleosides; D000099227:Abacavir; C057503:carbovir; C401943:gamma-lactamase
keywords: (+)-γ-Lactamase; 2-Azabicyclo[2.2.1]hept-5-en-3-one; Enzymatic resolution; Site-specific mutagenesis