Construction of an optimized Escherichia coli strain able to produce prenylflavonoids

Abstract

Prenylflavonoids are flavonoid derived compounds with a lipophilic prenyl side-chain. Microbial cell factories offer an efficient and cheap production method to obtain these relevant compounds. This study designed and validated a biosynthetic pathway to produce prenylnaringenins in Escherichia coli for the first time. Firstly, tyrosine ammonia-lyase, 4-coumarate-CoA ligase, chalcone synthase, and chalcone isomerase were expressed to produce the intermediate naringenin (689.5 mg/L). Afterwards, different prenyltransferase (PT) from different sources were expressed to produce prenylnaringenins in the optimized strain. Since the PT extended substrate (dimethylallyl pyrophosphate-DMAPP) is limiting, synthetic biology approaches were used to construct a boosted DMAPP-E. coli strain. Experiments using naringenin and glucose as substrate showed that prenylnaringenins were successfully produced. This work represents a significant step towards de novo production of prenylflavonoids in E. coli.