The metabolism of (R)-3-hydroxybutyrate is regulated by the enhancer-binding protein PA2005 and the alternative sigma factor RpoN in Pseudomonas aeruginosa PAO1

Microbiology (Reading). 2015 Nov;161(Pt 11):2232-42. doi: 10.1099/mic.0.000163. Epub 2015 Aug 25.


A variety of soil-dwelling bacteria produce polyhydroxybutyrate (PHB), which serves as a source of energy and carbon under nutrient deprivation. Bacteria belonging to the genus Pseudomonas do not generally produce PHB but are capable of using the PHB degradation product (R)-3-hydroxybutyrate [(R)-3-HB] as a growth substrate. Essential to this utilization is the NAD+-dependent dehydrogenase BdhA that converts (R)-3-HB into acetoacetate, a molecule that readily enters central metabolism. Apart from the numerous studies that had focused on the biochemical characterization of BdhA, there was nothing known about the assimilation of (R)-3-HB in Pseudomonas, including the genetic regulation of bdhA expression. This study aimed to define the regulatory factors that govern or dictate the expression of the bdhA gene and (R)-3-HB assimilation in Pseudomonas aeruginosa PAO1. Importantly, expression of the bdhA gene was found to be specifically induced by (R)-3-HB in a manner dependent on the alternative sigma factor RpoN and the enhancer-binding protein PA2005.This mode of regulation was essential for the utilization of (R)-3-HB as a sole source of energy and carbon. However, non-induced levels of bdhA expression were sufficient for P. aeruginosa PAO1 to grow on ( ± )-1,3-butanediol, which is catabolized through an (R)-3-HB intermediate. Because this is, we believe, the first report of an enhancer-binding protein that responds to (R)-3-HB, PA2005 was named HbcR for (R)-3-hydroxybutyrate catabolism regulator.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid / metabolism*
  • Acetoacetates / metabolism
  • Bacterial Proteins / metabolism*
  • Butylene Glycols / metabolism
  • Carbon / metabolism
  • DNA-Binding Proteins / metabolism*
  • Energy Metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial*
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism*
  • RNA Polymerase Sigma 54 / metabolism*


  • Acetoacetates
  • Bacterial Proteins
  • Butylene Glycols
  • DNA-Binding Proteins
  • 1,3-butylene glycol
  • acetoacetic acid
  • Carbon
  • RNA Polymerase Sigma 54
  • 3-Hydroxybutyric Acid