Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase

J Biotechnol. 2015 Aug 20:208:37-43. doi: 10.1016/j.jbiotec.2015.05.012. Epub 2015 May 27.

Abstract

In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline.

Keywords: Biotransformation; Lactococcus lactis; Whole-cell biocatalysis; l-Arginine; l-Citrulline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry*
  • Bacterial Proteins* / biosynthesis
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Citrulline / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Guanidine / chemistry*
  • Hydrolases* / biosynthesis
  • Hydrolases* / chemistry
  • Hydrolases* / genetics
  • Lactococcus lactis* / enzymology
  • Lactococcus lactis* / genetics
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • Citrulline
  • Arginine
  • Hydrolases
  • arginine deiminase
  • Guanidine