Multienzyme cascade for synthesis of hydroxytyrosol via engineered Escherichia coli

Sci Rep. 2025 Jan 2;15(1):471. doi: 10.1038/s41598-024-84624-5.

Abstract

Hydroxytyrosol, a fine chemical, is widely utilized in food and pharmaceutical industries. In this study, we constructed a pathway to produce hydroxytyrosol by co-expressing tyrosin-phenol lyase (TPL), L-amino acid dehydrogenase (aadL), α-keto acid decarboxylase (KAD), aldehyde reductase (yahK) and glucose dehydrogenase (gdh). We changed combinations between plasmids with different copy numbers and target genes, resulting in 84% increase in hydroxytyrosol production. The yield of hydroxytyrosol was further increased 89.3% by optimizing the temperature and pH. Finally, 55.3 mM hydroxytyrosol was produced within 14 h by fed-batch biotransformation. This study provides a novel approach for hydroxytyrosol production.

Keywords: Escherichia coli; Cascade reaction; Hydroxytyrosol; Whole cell biotransformation.

MeSH terms

  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Glucose 1-Dehydrogenase / genetics
  • Glucose 1-Dehydrogenase / metabolism
  • Hydrogen-Ion Concentration
  • Metabolic Engineering* / methods
  • Phenylethyl Alcohol* / analogs & derivatives
  • Phenylethyl Alcohol* / metabolism
  • Plasmids / genetics
  • Plasmids / metabolism
  • Temperature
  • Tyrosine Phenol-Lyase / genetics
  • Tyrosine Phenol-Lyase / metabolism

Substances

  • Phenylethyl Alcohol
  • 3,4-dihydroxyphenylethanol
  • Tyrosine Phenol-Lyase
  • Glucose 1-Dehydrogenase