title: Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives.
abstract: Plants produce a variety of natural products with promising biological activities, such as the phenylpropanoids resveratrol and curcumin. While these molecules are naturally assembled through dedicated plant metabolic pathways, combinatorial biosynthesis has become an attractive tool to generate desired molecules. In this work, we demonstrated that biosynthetic enzymes from different sources can be recombined like legos to make various molecules. Seven biosynthetic genes from plants and bacteria were used to establish a variety of complete biosynthetic pathways in Escherichia coli to make valuable compounds. Different combinations of these biosynthetic bricks were made to design rationally various natural product pathways, yielding four phenylpropanoid acids (cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid), three bioactive natural stilbenoids (resveratrol, piceatannol and pinosylvin), and three natural curcuminoids (curcumin, bisdemethoxycurcumin and dicinnamoylmethane). A curcumin analog dicaffeoylmethane was synthesized by removing a methyltransferase from the curcumin biosynthetic pathway. Furthermore, introduction of a fungal flavin-dependent halogenase into the resveratrol biosynthetic pathway yielded a novel chlorinated molecule 2-chloro-resveratrol. This work thus provides a novel and efficient biosynthetic approach to creating various bioactive molecules. Further expansion of the library of the biosynthetic bricks will provide a resource for rational design of various phenylpropanoids via the combinatorial biosynthesis approach.
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, College of Bioengineering, Jimei University, 43 Yindou Road, Xiamen, Fujian 361021, China.
authors.forename: Anfeng
authors.initials: A
authors.lastname: Xiao
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
authors.forename: Micah
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Skidmore
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA. Electronic address: jixun.zhan@usu.edu.
authors.forename: Jixun
authors.initials: J
authors.lastname: Zhan
mesh_terms: D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D060847:Metabolic Engineering; D010666:Phenylpropionates / Q000378:metabolism*
chemical_list: D010666:Phenylpropionates
keywords: Biosynthetic bricks; Combinatorial biosynthesis; Escherichia coli; Heterologous host; Plant phenylpropanoids