UV mutagenesis of Cupriavidus necator for extracellular production of (R)-3-hydroxybutyric acid

J Appl Microbiol. 2008 Jul;105(1):236-42. doi: 10.1111/j.1365-2672.2008.03774.x. Epub 2008 Apr 9.

Abstract

Aim: Ultraviolet (UV) mutagenesis was carried out to obtain mutant strains of Cupriavidus necator that could produce (R)-3-hydroxybutyric acid [(R)-3-HB] in the culture supernatant.

Methods and results: C. necator (formerly known as Ralstonia eutropha) was subjected to UV radiation to generate mutants that are capable of producing (R)-3-HB in the culture supernatant. Results indicated that UV mutagen disrupted the phbB (phbB knock-out) and thus, promoted production of (R)-3-HB in mutant strains. Inclusion of acetoacetate esters (carbonyl compounds) in the culture broth led to increased production of (R)-3-HB. Thus, acetoacetyl-CoA (an intermediate of the PHB synthetic pathway) might have been converted to acetoacetate, which in the presence of (R)-3-HB dehydrogenase and NADPH/NADP(+), resulted in extracellular production of (R)-3-HB.

Conclusions: UV mutagenesis proved to be a satisfactory method in generating interesting mutants for extracellular production of (R)-3-HB. Extracellular production of (R)-3-HB upon addition of acetoacetate esters would suggest a likely (R)-3-HB biosynthetic pathway in C. necator.

Significance and impact of the study: Mutants obtained in this study are very useful for production of (R)-3-HB. For the first time, the production of (R)-3-HB by C. necator via acetoacetate is reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / analysis
  • 3-Hydroxybutyric Acid / metabolism*
  • Bioreactors / microbiology
  • Chromatography, High Pressure Liquid
  • Cupriavidus necator / genetics
  • Cupriavidus necator / metabolism
  • Cupriavidus necator / radiation effects*
  • Industrial Microbiology / methods*
  • Mutagenesis*
  • Spectrophotometry
  • Ultraviolet Rays*

Substances

  • 3-Hydroxybutyric Acid