Increasement of O-acetylhomoserine production in Escherichia coli by modification of glycerol-oxidative pathway coupled with optimization of fermentation

Biotechnol Lett. 2021 Jan;43(1):105-117. doi: 10.1007/s10529-020-03031-8. Epub 2020 Oct 20.

Abstract

Objective: O-acetylhomoserine (OAH) is an important platform chemical to produce high-valuable chemicals. To improve the production of O-acetylhomoserine from glycerol, the glycerol-oxidative pathway was investigated and the optimization of fermentation with crude glycerol was carried out.

Results: The glycerol-uptake system and glycerol-oxidative pathway were modified and O-acetyltransferase from Corynebacterium glutamicum was introduced into the engineered strain to produce O-acetylhomoserine. It was found that overexpression of glycerol 3-phosphate dehydrogenase improved the OAH production to 6.79 and 4.21 g/L from pure and crude glycerol, respectively. And the higher OAH production depending on higher level of transcription of glpD. Two-step statistical approach was employed to optimize the fermentation conditions. The significant effects of glycerol, ammonium chloride and yeast extract were screened applying Plackett-Burman design and were optimized further by employing the Response Surface Methodology. Under optimized conditions, the OAH production was up to 9.42 and 7.01 g/L when pure and crude glycerol were used in shake flask cultivations, respectively.

Conclusions: The enzymatic step catalyzing the oxidation of glycerol through GlpD was the key step for OAH production, which served the foundation for realization of a consistent OAH production from crude glycerol in the future.

Keywords: Expression regulation; Glycerol utilization; O-acetylhomoserine; Optimization; Response surface methodology.

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Corynebacterium glutamicum / enzymology
  • Corynebacterium glutamicum / genetics
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Fermentation / genetics
  • Glycerol / metabolism*
  • Homoserine* / analogs & derivatives
  • Homoserine* / analysis
  • Homoserine* / genetics
  • Homoserine* / metabolism
  • Metabolic Engineering / methods*
  • Metabolic Networks and Pathways / genetics
  • Oxidation-Reduction

Substances

  • Bacterial Proteins
  • Homoserine
  • Acetyltransferases
  • Glycerol