Production of (R)-3-quinuclidinol by E. coli biocatalysts possessing NADH-dependent 3-quinuclidinone reductase (QNR or bacC) from Microbacterium luteolum and Leifsonia alcohol dehydrogenase (LSADH)

Int J Mol Sci. 2012 Oct 19;13(10):13542-53. doi: 10.3390/ijms131013542.

Abstract

We found two NADH-dependent reductases (QNR and bacC) in Microbacterium luteolum JCM 9174 (M. luteolum JCM 9174) that can reduce 3-quinuclidinone to optically pure (R)-(-)-3-quinuclidinol. Alcohol dehydrogenase from Leifsonia sp. (LSADH) was combined with these reductases to regenerate NAD+ to NADH in situ in the presence of 2-propanol as a hydrogen donor. The reductase and LSADH genes were efficiently expressed in E. coli cells. A number of constructed E. coli biocatalysts (intact or immobilized) were applied to the resting cell reaction and optimized. Under the optimized conditions, (R)-(-)-3-quinuclidinol was synthesized from 3-quinuclidinone (15% w/v, 939 mM) giving a conversion yield of 100% for immobilized QNR. The optical purity of the (R)-(-)-3-quinuclidinol produced by the enzymatic reactions was >99.9%. Thus, E. coli biocatalysis should be useful for the practical production of the pharmaceutically important intermediate, (R)-(-)-3-quinuclidinol.

MeSH terms

  • Actinomycetales / enzymology*
  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism*
  • Biocatalysis
  • Escherichia coli / metabolism*
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • Optical Rotation
  • Quinuclidines / chemistry
  • Quinuclidines / metabolism*
  • Stereoisomerism
  • Time Factors

Substances

  • Quinuclidines
  • 3-quinuclidinol
  • Alcohol Dehydrogenase
  • NADH, NADPH Oxidoreductases