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Exploring recombinant flavonoid biosynthesis in metabolically engineered Escherichia coli

Chembiochem. 2004 Apr 2;5(4):500-7. doi: 10.1002/cbic.200300783.

Abstract

Flavonoids are important plant-specific secondary metabolites synthesized from 4-coumaroyl coenzyme A (CoA), derived from the general phenylpropanoid pathway, and three malonyl-CoAs. The synthesis involves a plant type III polyketide synthase, chalcone synthase. We report the cloning and coexpression in Escherichia coli of phenylalanine ammonia lyase, cinnamate-4-hydroxylase, 4-coumarate:CoA ligase, and chalcone synthase from the model plant Arabidopsis thaliana. Simultaneous expression of all four genes resulted in a blockage after the first enzymatic step caused by the presence of nonfunctional cinnamate-4-hydroxylase. To overcome this problem we fed exogenous 4-coumaric acid to induced cultures. We observed high-level production of the flavanone naringenin as a result. We were also able to produce phloretin by feeding cultures with 3-(4-hydroxyphenyl)propionic acid. Feeding with ferulic or caffeic acid did not yield the corresponding flavanones. We have also cloned and partially characterized a new tyrosine ammonia lyase from Rhodobacter sphaeroides. Tyrosine ammonia lyase was substituted for phenylalanine ammonia lyase and cinnamate-4-hydroxylase in our E. coli clones and three different growth media were tested. After 48 h induction, high-level production (20.8 mg L(-1)) of naringenin in metabolically engineered E. coli was observed for the first time.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arabidopsis* / enzymology
  • Arabidopsis* / genetics
  • Arabidopsis* / metabolism
  • Cell Division / drug effects
  • Chromatography, High Pressure Liquid
  • Coumaric Acids / pharmacology
  • Culture Media, Conditioned / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Flavanones / biosynthesis
  • Flavanones / chemistry
  • Flavanones / metabolism
  • Flavonoids / biosynthesis*
  • Flavonoids / chemistry
  • Flavonoids / metabolism
  • Genetic Engineering*
  • Molecular Structure
  • Phenylpropionates / pharmacology
  • Plasmids / genetics
  • Propionates

Substances

  • Coumaric Acids
  • Culture Media, Conditioned
  • Flavanones
  • Flavonoids
  • Phenylpropionates
  • Propionates
  • phloretic acid
  • naringenin
  • p-coumaric acid