title: Multivariate modular metabolic engineering of Escherichia coli to produce resveratrol from L-tyrosine.
abstract: Microbial fermentations and bioconversion promise to revolutionize the conventional extraction of resveratrol from natural plant sources. However, the development of efficient and feasible microbial processes remains challenging. Current fermentation strategies often require supplementation of expensive phenylpropanoic precursors and two separate fermentation protocols, which are significantly more difficult and expensive to undertake when migrating to large-scale fermentation processes. In this study, an Escherichia coli fermentation system, consisting of tyrosine ammonia lyase (TAL), 4-coumarate:CoA ligase (4CL), stilbene synthase (STS), malonate synthetase, and malonate carrier protein, was developed to produce resveratrol from L-tyrosine. Multivariate modular metabolic engineering, which redefined the overall pathway as a collection of distinct modules, was employed to assess and alleviate pathway bottlenecks. Using this strategy, the optimum strain was capable of producing 35.02 mg/L of resveratrol from L-tyrosine in a single medium. The strategy described here paves the way to the development of a simple and economical process for microbial production of resveratrol and other similar stilbene chemicals.
authors.affiliation: Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Wu
authors.forename: Peiran
authors.initials: P
authors.lastname: Liu
authors.forename: Yongming
authors.initials: Y
authors.lastname: Fan
authors.forename: Han
authors.initials: H
authors.lastname: Bao
authors.forename: Guocheng
authors.initials: G
authors.lastname: Du
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000642:Ammonia-Lyases / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D003373:Coumaric Acids / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005285:Fermentation; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways; D015999:Multivariate Analysis; D011422:Propionates; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D003373:Coumaric Acids; D029968:Escherichia coli Proteins; D011422:Propionates; D013267:Stilbenes; D014443:Tyrosine; D000217:Acyltransferases; C022674:stilbene synthase; D000642:Ammonia-Lyases; C023208:L-tyrosine ammonia-lyase; D003066:Coenzyme A Ligases; C019943:4-coumarate-CoA ligase; C495469:p-coumaric acid; D000077185:Resveratrol
keywords: Pathway optimization; Phenylpropanoids; Plant natural products; Stilbene; Synthetic biology