Novel one-pot ATP regeneration system based on three-enzyme cascade for industrial CTP production

Biotechnol Lett. 2017 Dec;39(12):1875-1881. doi: 10.1007/s10529-017-2427-x. Epub 2017 Aug 31.

Abstract

Objectives: To develop a new one-pot polyphosphate kinase (PPK) system with low cost and high efficiency for ATP regeneration in industrial CTP production.

Results: We developed a new one-pot PPK system by applying a three-enzyme cascade (CMK, NDK and PPK) with an in vitro polyP-based ATP regeneration system. The PPK was selected from twenty sources, and was made solvable by fusion expressing with soluble protein and constructing polycistronic plasmids, or co-expressing with molecular chaperones GroES/EL. Activities of other enzymes were optimized by employing fusion expression, tac-pBAD system, Rosetta host and codon optimization. After 24 h, the concentration of CDP and CTP reached 3.8 ± 0.2 and 6.9 ± 0.3 mM l-1 respectively with a yield of approximately 79%. The molar conversion rate of CTP was 51%, and its yield and conversion rate increased 100% from the traditional system.

Conclusions: A new one-pot ATP regeneration system applying polyphosphate kinase for CTP production was developed.

Keywords: ATP regeneration system; CTP production; Fusion expression; Molecular chaperone; Polyphosphate kinase.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Bioreactors / microbiology
  • Cytidine Triphosphate / analysis
  • Cytidine Triphosphate / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Metabolic Engineering
  • Phosphotransferases (Phosphate Group Acceptor) / genetics
  • Phosphotransferases (Phosphate Group Acceptor) / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*

Substances

  • Recombinant Fusion Proteins
  • Cytidine Triphosphate
  • Adenosine Triphosphate
  • Phosphotransferases (Phosphate Group Acceptor)
  • polyphosphate kinase