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Optimizing bioconversion pathways through systems analysis and metabolic engineering.


ABSTRACT: 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.

SUBMITTER: Stafford DE 

PROVIDER: S-EPMC122274 | biostudies-literature | 2002 Feb

REPOSITORIES: biostudies-literature

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Optimizing bioconversion pathways through systems analysis and metabolic engineering.

Stafford Daniel E DE   Yanagimachi Kurt S KS   Lessard Philip A PA   Rijhwani Sushil K SK   Sinskey Anthony J AJ   Stephanopoulos Gregory G  

Proceedings of the National Academy of Sciences of the United States of America 20020201 4


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 precur  ...[more]

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