Optimizing bioconversion pathways through systems analysis and metabolic engineering

Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1801-6. doi: 10.1073/pnas.032681699.


We demonstrate a general approach for metabolic engineering of biocatalytic systems comprising the uses of a chemostat for strain improvement and radioisotopic tracers for the quantification of pathway fluxes. Flux determination allows the identification of target pathways for modification as validated by subsequent overexpression of the corresponding gene. We demonstrate this method in the indene bioconversion network of Rhodococcus modified for the overproduction of 1,2-indandiol, a key precursor for the AIDS drug Crixivan.

Publication types

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

MeSH terms

  • Biomedical Engineering / methods*
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Drug Industry*
  • Epoxide Hydrolases / metabolism
  • Fermentation
  • Genetic Engineering
  • Hydrolysis
  • Indans / chemistry
  • Indans / metabolism
  • Indenes / chemistry
  • Indenes / metabolism
  • Metabolism
  • Models, Chemical
  • Plasmids / metabolism
  • Rhodococcus / metabolism
  • Systems Analysis
  • Time Factors


  • Indans
  • Indenes
  • 1,2-indanediol
  • Epoxide Hydrolases