title: Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway.
abstract: Salvianic acid A, a valuable derivative from L-tyrosine biosynthetic pathway of the herbal plant Salvia miltiorrhiza, is well known for its antioxidant activities and efficacious therapeutic potential on cardiovascular diseases. Salvianic acid A was traditionally isolated from plant root or synthesized by chemical methods, both of which had low efficiency. Herein, we developed an unprecedented artificial biosynthetic pathway of salvianic acid A in E. coli, enabling its production from glucose directly. In this pathway, 4-hydroxyphenylpyruvate was converted to salvianic acid A via D-lactate dehydrogenase (encoding by d-ldh from Lactobacillus pentosus) and hydroxylase complex (encoding by hpaBC from E. coli). Furthermore, we optimized the pathway by a modular engineering approach and deleting genes involved in the regulatory and competing pathways. The metabolically engineered E. coli strain achieved high productivity of salvianic acid A (7.1g/L) with a yield of 0.47mol/mol glucose.
authors.affiliation: Key Laboratory of Systems Bioengineering, Ministry of Education; Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, P.O. Box 6888, Tianjin 300072, China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Yao
authors.forename: Chang-Song
authors.initials: CS
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qiao
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Zhao
mesh_terms: D002109:Caffeic Acids / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D045022:Lactate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D007773:Lactates / Q000378:metabolism*; D007778:Lactobacillus / Q000201:enzymology / Q000235:genetics; D060847:Metabolic Engineering; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics; D018517:Plant Roots / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D007773:Lactates; C066201:salvianolic acid A; D006899:Mixed Function Oxygenases; D045022:Lactate Dehydrogenases; C071195:D-lactate dehydrogenase; C026252:4-hydroxyphenylacetate 3-monooxygenase; D005947:Glucose
keywords: D-lactate dehydrogenase; Escherichia coli; Metabolic engineering; Salvianic acid A; hpaBC