The putative malate/lactate dehydrogenase from Pseudomonas putida is an NADPH-dependent delta1-piperideine-2-carboxylate/delta1-pyrroline-2-carboxylate reductase involved in the catabolism of D-lysine and D-proline

J Biol Chem. 2005 Feb 18;280(7):5329-35. doi: 10.1074/jbc.M411918200. Epub 2004 Nov 23.

Abstract

A Pseudomonas putida ATCC12633 gene, dpkA, encoding a putative protein annotated as malate/L-lactate dehydrogenase in various sequence data bases was disrupted by homologous recombination. The resultant dpkA(-) mutant was deprived of the ability to use D-lysine and also D-proline as a sole carbon source. The dpkA gene was cloned and overexpressed in Escherichia coli, and the gene product was characterized. The enzyme showed neither malate dehydrogenase nor lactate dehydrogenase activity but catalyzed the NADPH-dependent reduction of such cyclic imines as Delta(1)-piperideine-2-carboxylate and Delta(1)-pyrroline-2-carboxylate to form L-pipecolate and L-proline, respectively. NADH also served as a hydrogen donor for both substrates, although the reaction rates were less than 1% of those with NADPH. The reverse reactions were also catalyzed by the enzyme but at much lower rates. Thus, the enzyme has dual metabolic functions, and we named the enzyme Delta(1)-piperideine-2-carboxylate/Delta(1)-pyrroline-2-carboxylate reductase, the first member of a novel subclass in a large family of NAD(P)-dependent oxidoreductases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Chromatography, High Pressure Liquid
  • Coenzymes / metabolism
  • Evolution, Molecular
  • Hydrogen-Ion Concentration
  • Kinetics
  • L-Lactate Dehydrogenase / metabolism*
  • Lysine / metabolism*
  • Malate Dehydrogenase / metabolism
  • NADP / metabolism*
  • Pipecolic Acids / metabolism*
  • Proline / metabolism*
  • Pseudomonas putida / enzymology*
  • Pseudomonas putida / genetics
  • Pyrroline Carboxylate Reductases / antagonists & inhibitors
  • Pyrroline Carboxylate Reductases / genetics
  • Pyrroline Carboxylate Reductases / metabolism*
  • Substrate Specificity
  • Temperature

Substances

  • Bacterial Proteins
  • Coenzymes
  • Pipecolic Acids
  • delta(1)-piperidine-2-carboxylic acid
  • NADP
  • Proline
  • L-Lactate Dehydrogenase
  • Malate Dehydrogenase
  • Pyrroline Carboxylate Reductases
  • Lysine