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  • Construction of a Corynebac...
    Kallscheuer, Nicolai; Vogt, Michael; Stenzel, Anton; Gätgens, Jochem; Bott, Michael; Marienhagen, Jan

    Metabolic engineering, November 2016, 2016-11-00, 20161101, Letnik: 38
    Journal Article

    Corynebacterium glutamicum is an important organism in industrial biotechnology for the microbial production of bulk chemicals, in particular amino acids. However, until now activity of a complex catabolic network for the degradation of aromatic compounds averted application of C. glutamicum as production host for aromatic compounds of pharmaceutical or biotechnological interest. In the course of the construction of a suitable C. glutamicum platform strain for plant polyphenol production, four gene clusters comprising 21 genes involved in the catabolism of aromatic compounds were deleted. Expression of plant-derived and codon-optimized genes coding for a chalcone synthase (CHS) and a chalcone isomerase (CHI) in this strain background enabled formation of 35mg/L naringenin and 37mg/L eriodictyol from the supplemented phenylpropanoids p-coumaric acid and caffeic acid, respectively. Furthermore, expression of genes coding for a 4-coumarate: CoA-ligase (4CL) and a stilbene synthase (STS) led to the production of the stilbenes pinosylvin, resveratrol and piceatannol starting from supplemented phenylpropanoids cinnamic acid, p-coumaric acid and caffeic acid, respectively. Stilbene concentrations of up to 158mg/L could be achieved. Additional engineering of the amino acid metabolism for an optimal connection to the synthetic plant polyphenol pathways enabled resveratrol production directly from glucose. The construction of these C. glutamicum platform strains for the synthesis of plant polyphenols opens the door towards the microbial production of high-value aromatic compounds from cheap carbon sources with this microorganism. •Construction of a C. glutamicum strain unable to catabolize aromatic compounds.•Recombinant C. glutamicum strain synthesizes three stilbenes from phenylpropanoids.•Plant polyphenols can be produced from glucose without precursor supplementation.•Production of (2S)-flavanones as direct flavonoid precursors.•Strain offers huge potential for future production of high-value aromatic compounds.