Biosynthesis of resveratrol using metabolically engineered Escherichia coli

Jin Yeong Park,Joong-Hoon Ahn,Bong-Gyu Kim,Jeong-Hyeon Lim

doi:10.1186/s13765-021-00595-5

Abstract

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a phenolic compound widely used in pharmaceutics and nutraceutics. Although resveratrol is produced by some plant species, including grapes, peanuts, and berries, the content of resveratrol and its derivatives are very low. Therefore, an alternative biosynthetic method using microorganisms, such as Escherichia coli, has been developed over the past two decades. In the present study, a resveratrol-over-producing E. coli strain was developed using three strategies. First, we increased the synthesis of p-coumaric acid, a precursor of resveratrol, by manipulating genes in the shikimate pathway of E. coli. Second, three genes involved in resveratrol biosynthesis, such as tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and stilbene synthase (STS), were cloned from diverse sources, such as plants and microorganisms, and the best combination was selected to maximize resveratrol production in E. coli. Finally, culture conditions, such as cell concentration, culture temperature, and carbon sources, were established for optimal resveratrol production. Through these strategies, approximately 80.4 mg/L of resveratrol was biosynthesized after 48 h of culture using glycerol as a carbon source.

Highlights

Polyphenols are plant secondary metabolites and valuable sources for the development of cosmetic materials, functional food ingredients, and pharmaceuticals [1,2,3]
Polyphenols are generally derived through the phenylpropanoid pathway [4]. Depending on their carbon skeleton, they can be classified into four classes, such as phenolic acids including gallic acid and salicylic acid composed of C6-C1 skeleton, hydroxycinnamic acid including cinnamic acid, p-coumaric acid, and caffeic acid composed of C6-C3 skeleton, stilbene including resveratrol, piceatannol, and pallidol composed of C6-C2-C6 skeleton, flavonoids including naringenin, quercetin, and genistein composed of C6-C3-C6 skeleton [4,5,6]
Production of resveratrol in E. coli from p‐coumaric acid To synthesize resveratrol from glucose in E. coli, at least three genes, namely tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and STS are necessary (Fig. 1)

Summary

Introduction

Polyphenols are plant secondary metabolites and valuable sources for the development of cosmetic materials, functional food ingredients, and pharmaceuticals [1,2,3]. Polyphenols are generally derived through the phenylpropanoid pathway [4] Depending on their carbon skeleton, they can be classified into four classes, such as phenolic acids including gallic acid and salicylic acid composed of C6-C1 skeleton, hydroxycinnamic acid including cinnamic acid, p-coumaric acid, and caffeic acid composed of C6-C3 skeleton, stilbene including resveratrol, piceatannol, and pallidol composed of C6-C2-C6 skeleton, flavonoids including naringenin, quercetin, and genistein composed of C6-C3-C6 skeleton [4,5,6]. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic compound containing a C6-C2-C6 skeleton. It is synthesized naturally in several plants in response to pathogenic fungi and bacteria or wounds caused by insects and herbivores [7,8,9]. Trans-cinnamic acid is converted into p-coumaric acid

Methods

Results

Conclusion