| Title | Optimizing bioconversion pathways through systems analysis and metabolic engineering. |
| Publication Type | Journal Article |
| Year of Publication | 2002 |
| Authors | Stafford, DE, Yanagimachi, KS, Lessard, PA, Rijhwani, SK, Sinskey, AJ, Stephanopoulos, G |
| Journal | Proc Natl Acad Sci U S A |
| Volume | 99 |
| Issue | 4 |
| Pagination | 1801-6 |
| Date Published | 2002 Feb 19 |
| ISSN | 0027-8424 |
| Keywords | Biomedical Engineering, Catalysis, Chromatography, High Pressure Liquid, Drug Industry, Epoxide Hydrolases, Fermentation, Genetic Engineering, Hydrolysis, Indans, Indenes, Metabolism, Models, Chemical, Plasmids, Rhodococcus, Systems Analysis, Time Factors |
| 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. |
| DOI | 10.1073/pnas.032681699 |
| Alternate Journal | Proc Natl Acad Sci U S A |
| Citation Key | 204 |
| PubMed ID | 11854482 |
| PubMed Central ID | PMC122274 |
| Grant List | T32 GM008334 / GM / NIGMS NIH HHS / United States 2T32 GM08334-10 / GM / NIGMS NIH HHS / United States |