Biosynthesis of (R)-(+)-perillyl alcohol by Escherichia coli expressing neryl pyrophosphate synthase

Chao Sun; Rubing Zhang; Congxia Xie

doi:10.1002/elsc.202100135

Biosynthesis of (R)-(+)-perillyl alcohol by Escherichia coli expressing neryl pyrophosphate synthase

Eng Life Sci. 2022 Feb 13;22(5):407-416. doi: 10.1002/elsc.202100135. eCollection 2022 May.

Authors

Chao Sun^{1

2}, Rubing Zhang², Congxia Xie¹

Affiliations

¹ State Key Laboratory Base of Eco-Chemical Engineering, College of Chemistry and Molecular Engineering Qingdao University of Science and Technology Qingdao P. R. China.
² CAS Key Laboratory of Bio-based Materials Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences Qingdao P. R. China.

Abstract

(R)-(+)-perillyl alcohol is widely used in agricultural and anticarcinogenic fields. Microbial production of (R)-(+)-perillyl alcohol was investigated in this study. We optimized biosynthesis of (R)-(+)-perillyl alcohol in Escherichia coli by using neryl pyrophosphate synthase and NADPH regeneration. Engineering neryl pyrophosphate (NPP)-supplied pathway resulted in a 4-fold improvement of (R)-(+)-perillyl alcohol titer. Subsequently, combined engineering of p-cymene monooxygenase (CymA) expression and module for NADPH regeneration exhibited a 15.4-fold increase of titer over the initial strain S02. Finally, 453 mg/L (R)-(+)-perillyl alcohol was achieved in fed-batch fermentation, which is the highest (R)-(+)-perillyl alcohol titer in E. coli.

Keywords: (R)‐(+)‐perillyl alcohol; Escherichia coli; NADPH regeneration; neryl pyrophosphate synthase.