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Combinatorial Optimization of Resveratrol Production in Engineered E. coli.

Ying Zhao1,2,3, Bi-Han Wu1,2,3, Zhen-Ning Liu1,2,3

  • 1Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology , Tianjin University , Tianjin 300350 , China.

Journal of Agricultural and Food Chemistry
|November 30, 2018
PubMed
Summary

Engineered E. coli efficiently produces resveratrol, a valuable plant compound, by optimizing its biosynthetic pathway and cellular environment. This study enhances resveratrol production for nutraceutical applications.

Keywords:
Escherichia colicombinatorial optimizationintracellular environmentmetabolic engineeringresveratrolsynthetic biology

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Synthetic Biology

Background:

  • Resveratrol is a plant-derived polyphenol with diverse health benefits, widely used in nutraceuticals and food additives.
  • Efficient microbial production of resveratrol is crucial for meeting market demand and reducing reliance on plant extraction.

Purpose of the Study:

  • To enhance resveratrol biosynthesis and production in a heterologous Escherichia coli (E. coli) expression system.
  • To optimize the resveratrol biosynthetic pathway and intracellular environment for increased yield.

Main Methods:

  • Combinatorial optimization of resveratrol biosynthetic pathway genes screened from various species.
  • Enhancement of malonyl-CoA availability by expressing Corynebacterium glutamicum ACC and antisense inhibition of native fabD.
  • Transport engineering for resveratrol secretion and introduction of molecular chaperones to improve intracellular conditions.
  • Tuning the expression of key enzymes: PcTAL, At4CL, and VvSTS.

Main Results:

  • Initial construction of resveratrol-producing E. coli strains through gene screening and expression pattern analysis.
  • Significant increase in resveratrol biosynthesis by targeting malonyl-CoA availability and inhibiting fabD.
  • Engineered E. coli produced 57.77 mg/L of resveratrol from L-tyrosine with optimized enzyme expression.
  • Integrated strategies led to a final resveratrol titer of 238.71 mg/L from L-tyrosine.

Conclusions:

  • Combinatorial optimization of biosynthetic pathways and intracellular environments in E. coli is a viable strategy for producing valuable natural products.
  • The developed engineered E. coli strain demonstrates a promising platform for the high-yield production of resveratrol.
  • This study provides a foundation for the microbial production of other complex natural products.