title: A Novel Synthetic Pathway Enables Microbial Production of Polyphenols Independent from the Endogenous Aromatic Amino Acid Metabolism.
abstract: Numerous plant polyphenols have potential applications as pharmaceuticals or nutraceuticals. Stilbenes and flavonoids as most abundant polyphenols are synthesized from phenylpropanoids, which are exclusively derived from aromatic amino acids in nature. Several microorganisms were engineered for the synthesis of biotechnologically interesting plant polyphenols; however, low activity of heterologous ammonia lyases, linking endogenous microbial aromatic amino acid biosynthesis to phenylpropanoid synthesis, turned out to be the limiting step during microbial synthesis. We here developed an alternative strategy for polyphenol production from cheap benzoic acids by reversal of a β-oxidative phenylpropanoid degradation pathway avoiding any ammonia lyase activity. The synthetic pathway running in the non-natural direction is feasible with respect to thermodynamics and involved reaction mechanisms. Instantly, product titers of 5 mg/L resveratrol could be achieved in recombinant Corynebacterium glutamicum strains indicating that phenylpropanoid synthesis from 4-hydroxybenzoic acid can in principle be implemented independently from aromatic amino acids and ammonia lyase activity.
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich , D-52425 Jülich, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Kallscheuer
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich , D-52425 Jülich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vogt
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich , D-52425 Jülich, Germany.
authors.forename: Jan
authors.identifier: 0000-0001-5513-3730
authors.initials: J
authors.lastname: Marienhagen
mesh_terms: D024322:Amino Acids, Aromatic / Q000378:metabolism*; D001565:Benzoates / Q000378:metabolism; D001669:Biochemical Phenomena / Q000502:physiology; D001709:Biotechnology / Q000379:methods; D048230:Corynebacterium glutamicum / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods; D010226:Parabens / Q000378:metabolism; D010944:Plants / Q000378:metabolism; D059808:Polyphenols / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D024322:Amino Acids, Aromatic; D001565:Benzoates; D010226:Parabens; D059808:Polyphenols; C038193:4-hydroxybenzoic acid
keywords: Corynebacterium glutamicum; phenylpropanoids; plant secondary metabolites; resveratrol; reverse β-oxidation