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

Optimizing bioconversion pathways through systems analysis and metabolic engineering.

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  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.


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.

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