title: Construction of a chimeric biosynthetic pathway for the de novo biosynthesis of rosmarinic acid in Escherichia coli.
abstract: Hydroxycinnamic acid esters (HCEs) are widely-distributed phenylpropanoid-derived plant natural products. Rosmarinic acid (RA), the most well-known HCE, shows promise as a treatment for cancer and neurological disorders. In contrast to extraction from plant material or plant cell culture, microbial production of HCEs could be a sustainable, controlled means of production. Through the overexpression of a six-enzyme chimeric bacterial and plant pathway, we show the de novo biosynthesis of RA, and the related HCE isorinic acid (IA), in Escherichia coli. Probing the pathway through precursor supplementation showed several potential pathway bottlenecks. We demonstrated HCE biosynthesis using three plant rosmarinic acid synthase (RAS) orthologues, which exhibited different levels of HCE biosynthesis but produced the same ratio of IA to RA. This work serves as a proof-of-concept for a microbial production platform for HCEs by using a modular biosynthetic approach to access diverse natural and non-natural HCEs.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Avenue, St. Paul, MN 55108 (USA).
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bloch
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt-Dannert
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry / Q000378:metabolism; D002934:Cinnamates / Q000737:chemistry / Q000378:metabolism*; D003373:Coumaric Acids / Q000737:chemistry / Q000378:metabolism; D053630:Depsides / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D060847:Metabolic Engineering; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D010944:Plants / Q000201:enzymology / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D002109:Caffeic Acids; D002934:Cinnamates; D003373:Coumaric Acids; D053630:Depsides; D029968:Escherichia coli Proteins; D010940:Plant Proteins; D000097123:Rosmarinic Acid; C040048:caffeic acid
keywords: biosynthesis; hydroxycinnamic acid esters; metabolic engineering; natural products; rosmarinic acid