Asymmetric bio-epoxidation catalyzed with the styrene monooxygenase from Pseudomonas sp. LQ26

Yan Liu,Zhong-Liu Wu,Yu-Chang Liu

doi:10.1186/s40643-016-0087-7

Abstract

Styrene monooxygenases (SMOs) can catalyze the asymmetric epoxidation of alkenes to obtain optically active epoxides. This account describes a series of work of our group on the isolation, application, and improvement of an SMO from Pseudomonas sp. LQ26. The strain was isolated from an active sludge sample based on indigo-forming capacity. Then the gene encoding SMO was expressed in Escherichia coli, and the whole cells were applied in biocatalytic reactions. The substrate spectrum of SMO was successfully expanded from conjugated styrene derivatives to non-conjugated alkenes, especially α-substituted secondary allylic alcohols, affording enantiopure epoxides. Most significantly, cascade reactions involving ketoreductase and SMO were designed, which resulted in glycidol derivatives or epoxy ketones with excellent enantio- and diastereo-selectivity using α,β-unsaturated ketones as the substrates. In addition, mutants of SMO with altered substrate preference and enhanced activity were constructed, which indicated great potential of SMO for further improvement.

Highlights

Enantiopure epoxides are extremely versatile building blocks in organic synthesis and pharmaceutical industry (Lin et al 2011a; Sharpless 2002)
Numerous chemo-catalyzed asymmetric epoxidations have been developed in the last few decades, biocatalytic epoxidation serves as a strong candidate for preparing single enantiomeric epoxides, especially starting from nonfunctional terminal alkenes
Besides the two-component SMOs, several self-sufficient one-component SMOs have been isolated from Rhodococcus opacus (Tischler et al 2012), and a novel styrene monooxygenase SmoA isolated from metagenome as well (Van Hellemond et al 2007)

Summary

Introduction

Enantiopure epoxides are extremely versatile building blocks in organic synthesis and pharmaceutical industry (Lin et al 2011a; Sharpless 2002). Compared with classic chemo-catalysts and hydrolytic kinetic resolution to achieve optically pure styrene oxide, SMO catalyzes the epoxidation of styrene and derivatives with exquisite regio- and enantioselectives under moderate reaction conditions, providing an attracting alternative for the synthesis of chiral epoxides (Bernasconi et al 2000; Lin et al 2010; Schmid et al 2001). LQ26 showed a maximum of 79 % sequence identity with other styABs. It appeared as the most distant member of all SMOs originating from the genus of Pseudomonas (Lin et al 2010).

Results

Conclusion