Metabolically engineered cells for the production of resveratrol or an oligomeric or glycosidically-bound derivative thereof

摘要

A recombinant micro-organism producing resveratrol by a pathway in which phenylalanine ammonia lyase (PAL) produces trans-cinnamic acid from phenylalanine, cinnamate 4-hydroxylase (C4H) produces 4-coumaric acid from said trans-cinnamic acid, 4-coumarate-CoA ligase (4CL) produces 4-coumaroyl CoA from said 4-coumaric acid, and resveratrol synthase (VST) produces said resveratrol from said 4-coumaroyl CoA, or in which L-phenylalanine- or tyrosine-ammonia lyase (PAL/TAL) produces 4-coumaric acid, 4-coumarate-CoA ligase (4CL) produces 4-coumaroyl CoA from said 4-coumaric acid, and resveratrol synthase (VST) produces said resveratrol from said 4-coumaroyl CoA. The micro-organism may be a yeast, fungus or bacterium including Saccharomyces cerevisiae, E. coli, Lactococcus lactis, Aspergillus niger, or Aspergillus oryzae.

主权项

1. A method for producing resveratrol or an oligomeric or glycosidically-bound derivative thereof comprising:
a) cultivating a recombinant micro-organism comprising an engineered operative metabolic pathway producing resveratrol or an oligomeric or glycosidically-bound derivative thereof in a culture media comprising a carbon substrate from which the micro-organism can produce resveratrol, wherein the culture media does not require an external source of coumaric acid, and wherein the operative metabolic pathway produces:
i) 4-coumaric acid from L-phenylalanine catalysed by a phenylalanine ammonia lyase (PAL) and a cinnamate 4-hydroxylase (C4H) expressed in the micro-organism or from tyrosine catalysed by a phenylalanine ammonia lyase (PAL) or a tyrosine ammonia lyase (TAL) expressed in said micro-organism; andii) 4-coumaroyl-CoA from 4-coumaric acid catalysed by a 4-coumarate-CoA ligase (4CL) expressed in said micro-organism; andiii) resveratrol is produced from the 4-coumaroyl-CoA by a resveratrol synthase expressed in the micro-organism; and b) recovering the resveratrol or the oligomeric or glycosidically-bound derivative thereof from the culture media.