Resolution of biotin intermediate lactone by enzyme-catalyzed stereoselective lactonization in organic solvent

Abstract

A strain of Aspergillus oryzae WZ007 producing intracellular lipase with preference for the formation of the d-biotin intermediate lactone ((3 aS,6 aR)-tetrahydro-1,3-dibenzylhexahydro-1 H-Furo[3,4- d]imidazole-2,4-dione) 1 was screened from soil samples. The microbial cells fermented by the strain were used as biocatalysts after lyophilization, to resolve the racemic biotin intermediate lactone 1 by enantioselective lactonization in organic solvents. The enantioselective lactonization afforded optically active lactone 1 with high enantiomeric excess (e.e. ≥ 98%) and conversion ratio ( c ≥ 40%) when the biotransformation was carried out in dichloromethane. The e.e. of product was up to 99% after purification by inducing crystallization in acetone and basically satisfied the industrial application. The biosynthesis has been employed to produce kilograms supplies of optically active lactone 1 with high optical purity.