Development of novel and efficient biocatalytic systems for oxidoreductions in pharmaceutical synthesis

Abstract

Enzymatic oxidoreductions are very important biotransformations for efficient asymmetric synthesis, especially for the production of enantiopure compounds in pharmaceutical industry. However, the expensive cofactor NAD(P)H or NAD(P)+ which often required in enzymatic oxidoreductions need to be efficiently recycled for practical application; it is still difficult to obtain appropriate P450 monooxygenase with desired substrate specificity and high selectivity and to construct active recombinant biocatalysts via genetic engineering of P450 monooxygenase thus far; no practical example of tandem biocatalysts systems for enzymatic sequential oxidations has been published yet. In this thesis, several novel and efficient biocatalytic systems for oxidoreductions in pharmaceutical synthesis were developed, including bioreduction with efficient recycling of NADPH by coupled permeabilized microorganisms, regio- and stereo-selective biohydroxylations with a recombinant Escherichia coli expressing P450pyr monooxygenase of Sphingomonas sp. HXN-200, and the green and selective transformation of methylene to ketone via tandem biooxidations in one pot.