Efficient synthesis of the intermediate of abacavir and carbovir using a novel (+)-γ-lactamase as a catalyst

The enantiomers of 2-azabicyclo[2.2.1] hept-5-en-3-one (gamma-lactam) are key chiral synthons in the synthesis of antiviral drugs such as carbovir and abacavir. (+)-gamma-Lactamase can be used as a catalyst in the enzymatic preparation of optically pure (-)-gamma-lactam. Here, a (+)-gamma-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 gamma-lactam. The active site of the (+)-gamma-lactamase was studied by homologous modeling and molecular docking, and the accuracy of the prediction was confirmed by site-specific mutagenesis. The (+)-gamma-lactamase reveals the great practical potential as an enzymatic method for the efficient production of carbocyclic nucleosides of pharmaceutical interest. (C) 2015 Elsevier Ltd. All rights reserved.