Synthesis of citramalic acid from glycerol by metabolically engineered Escherichia coli

J Ind Microbiol Biotechnol. 2017 Oct;44(10):1483-1490. doi: 10.1007/s10295-017-1971-7. Epub 2017 Jul 25.

Abstract

Citramalic acid (citramalate) serves as a five-carbon precursor for the chemical synthesis of methacrylic acid. We compared citramalate and acetate accumulation from glycerol using Escherichia coli strains expressing a modified citramalate synthase gene cimA from Methanococcus jannaschii. These studies revealed that gltA coding citrate synthase, leuC coding 3-isopropylmalate dehydratase, and acetate pathway genes play important roles in elevating citramalate and minimizing acetate formation. Controlled 1.0 L batch experiments confirmed that deletions in all three acetate-production genes (poxB, ackA, and pta) were necessary to reduce acetate formation to less than 1 g/L during citramalate production from 30 g/L glycerol. Fed-batch processes using MEC568/pZE12-cimA (gltA leuC ackA-pta poxB) generated over 31 g/L citramalate and less than 2 g/L acetate from either purified or crude glycerol at yields exceeding 0.50 g citramalate/g glycerol in 132 h. These results hold promise for the viable formation of citramalate from unrefined glycerol.

Keywords: Acetate; Biodiesel; Citramalate synthase; Crude glycerol; Fed-batch.

MeSH terms

  • Acetates / metabolism
  • Acetyltransferases / metabolism
  • Batch Cell Culture Techniques
  • Biofuels
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Glycerol / metabolism*
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism
  • Malates / metabolism*
  • Metabolic Engineering*
  • Methanocaldococcus / enzymology
  • Methanocaldococcus / genetics

Substances

  • Acetates
  • Biofuels
  • Malates
  • Acetyltransferases
  • (R)-citramalate synthase
  • Hydro-Lyases
  • 3-isopropylmalate dehydratase
  • citramalate
  • Glycerol