An economically and environmentally acceptable synthesis of chiral drug intermediate L-pipecolic acid from biomass-derived lysine via artificially engineered microbes

J Ind Microbiol Biotechnol. 2018 Jun;45(6):405-415. doi: 10.1007/s10295-018-2044-2. Epub 2018 May 10.

Abstract

Deficiency in petroleum resources and increasing environmental concerns have pushed a bio-based economy to be built, employing a highly reproducible, metal contaminant free, sustainable and green biomanufacturing method. Here, a chiral drug intermediate L-pipecolic acid has been synthesized from biomass-derived lysine. This artificial bioconversion system involves the coexpression of four functional genes, which encode L-lysine α-oxidase from Scomber japonicus, glucose dehydrogenase from Bacillus subtilis, Δ1-piperideine-2-carboxylase reductase from Pseudomonas putida, and lysine permease from Escherichia coli. Besides, a lysine degradation enzyme has been knocked out to strengthen the process in this microbe. The overexpression of LysP improved the L-pipecolic acid titer about 1.6-folds compared to the control. This engineered microbial factory showed the highest L-pipecolic acid production of 46.7 g/L reported to date and a higher productivity of 2.41 g/L h and a yield of 0.89 g/g. This biotechnological L-pipecolic acid production is a simple, economic, and green technology to replace the presently used chemical synthesis.

Keywords: Artificial pathway; Biomanufacturing; L-Lysine; L-Pipecolic acid; Lysine permease.

MeSH terms

  • Amino Acid Oxidoreductases / chemistry
  • Bacillus subtilis / genetics
  • Biomass*
  • Chemistry, Pharmaceutical / economics
  • Chemistry, Pharmaceutical / methods*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Fermentation
  • Glucose 1-Dehydrogenase / genetics
  • Green Chemistry Technology / economics
  • Green Chemistry Technology / methods
  • Industrial Microbiology / economics
  • Industrial Microbiology / methods*
  • Lysine / chemistry*
  • Metabolic Engineering / economics
  • Metabolic Engineering / methods*
  • Pipecolic Acids / chemistry*
  • Plasmids / genetics
  • Pseudomonas putida / genetics
  • Stereoisomerism

Substances

  • Pipecolic Acids
  • Glucose 1-Dehydrogenase
  • Amino Acid Oxidoreductases
  • L-lysine oxidase
  • pipecolic acid
  • Lysine