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PubMed · 11854482

Optimizing bioconversion pathways through systems analysis and metabolic engineering.

Daniel E Stafford·Kurt S Yanagimachi·Philip A Lessard·Sushil K Rijhwani·Anthony J Sinskey·Gregory Stephanopoulos
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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.

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Biomedical EngineeringCatalysisChromatography, High Pressure LiquidDrug IndustryEpoxide HydrolasesFermentationGenetic EngineeringHydrolysisIndansIndenesMetabolismModels, ChemicalPlasmidsRhodococcusSystems AnalysisTime FactorsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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Daniel E Stafford, Kurt S Yanagimachi, Philip A Lessard, Sushil K Rijhwani, Anthony J Sinskey, Gregory Stephanopoulos. 2002-02-19. Optimizing bioconversion pathways through systems analysis and metabolic engineering.. https://doi.org/10.1073/pnas.032681699

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