Related Content
Search Google Scholar for:
|
|
Science 21 June 1991: Vol. 252. no. 5013, pp. 1675 - 1681 DOI: 10.1126/science.1904627
|
|
Articles
Science, Vol 252, Issue 5013, 1675-1681
Copyright © 1991 by American Association for the Advancement of Science
Network rigidity and metabolic engineering in metabolite overproduction
G Stephanopoulos
and
JJ Vallino
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist flux alterations at branch points. This problem can be addressed through the use of some general concepts of metabolic rigidity, which include a means for identifying and removing rigid branch points within an experimental framework.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- A new strategy for assessing sensitivities in biochemical models.
- S. Sahle, P. Mendes, S. Hoops, and U. Kummer (2008)
Phil Trans R Soc A
366, 3619-3631
| Abstract »
| Full Text »
| PDF »
- Exploiting Complexity and the Robustness of Network Architecture for Drug Discovery.
- M. K. Hellerstein (2008)
J. Pharmacol. Exp. Ther.
325, 1-9
| Abstract »
| Full Text »
| PDF »
- Metabolic engineering of a genetic selection system with tunable stringency.
- A. C. Kleeb, M. H. Edalat, M. Gamper, J. Haugstetter, L. Giger, M. Neuenschwander, P. Kast, and D. Hilvert (2007)
PNAS
104, 13907-13912
| Abstract »
| Full Text »
| PDF »
- Biology by design: reduction and synthesis of cellular components and behaviour.
- P. Marguet, F. Balagadde, C. Tan, and L. You (2007)
J R Soc Interface
4, 607-623
| Abstract »
| Full Text »
| PDF »
- Adaptive Evolution of Metabolic Pathways in Drosophila.
- J. Flowers, E Sezgin, S Kumagai, D. Duvernell, L. Matzkin, P. Schmidt, and W. Eanes (2007)
Mol. Biol. Evol.
24, 1347-1354
| Abstract »
| Full Text »
| PDF »
- Challenges in Engineering Microbes for Biofuels Production.
- G. Stephanopoulos (2007)
Science
315, 801-804
| Abstract »
| Full Text »
| PDF »
- Bayesian-based selection of metabolic objective functions.
- A. L. Knorr, R. Jain, and R. Srivastava (2007)
Bioinformatics
23, 351-357
| Abstract »
| Full Text »
| PDF »
- Tuning genetic control through promoter engineering.
- H. Alper, C. Fischer, E. Nevoigt, and G. Stephanopoulos (2005)
PNAS
102, 12678-12683
| Abstract »
| Full Text »
| PDF »
- Metabolic Engineering in the -omics Era: Elucidating and Modulating Regulatory Networks.
- G. N. Vemuri and A. A. Aristidou (2005)
Microbiol. Mol. Biol. Rev.
69, 197-216
| Abstract »
| Full Text »
| PDF »
- Understanding in Vivo Benzenoid Metabolism in Petunia Petal Tissue.
- J. Boatright, F. Negre, X. Chen, C. M. Kish, B. Wood, G. Peel, I. Orlova, D. Gang, D. Rhodes, and N. Dudareva (2004)
Plant Physiology
135, 1993-2011
| Abstract »
| Full Text »
| PDF »
- Osmotic Stress Response: Quantification of Cell Maintenance and Metabolic Fluxes in a Lysine-Overproducing Strain of Corynebacterium glutamicum.
- C. A. Varela, M. E. Baez, and E. Agosin (2004)
Appl. Envir. Microbiol.
70, 4222-4229
| Abstract »
| Full Text »
| PDF »
- A Functional Protein Chip for Pathway Optimization and in Vitro Metabolic Engineering.
- G. Y. Jung and G. Stephanopoulos (2004)
Science
304, 428-431
| Abstract »
| Full Text »
| PDF »
- The Metabolic Architecture of Plant Cells. STABILITY OF CENTRAL METABOLISM AND FLEXIBILITY OF ANABOLIC PATHWAYS DURING THE GROWTH CYCLE OF TOMATO CELLS.
- D. Rontein, M. Dieuaide-Noubhani, E. J. Dufourc, P. Raymond, and D. Rolin (2002)
J. Biol. Chem.
277, 43948-43960
| Abstract »
| Full Text »
| PDF »
- Intracellular Carbon Fluxes in Riboflavin-Producing Bacillussubtilis during Growth on Two-Carbon Substrate Mixtures.
- M. Dauner, M. Sonderegger, M. Hochuli, T. Szyperski, K. Wuthrich, H.-P. Hohmann, U. Sauer, and J. E. Bailey (2002)
Appl. Envir. Microbiol.
68, 1760-1771
| Abstract »
| Full Text »
| PDF »
- Carbon Flux Distribution and Kinetics of Cellulose Fermentation in Steady-State Continuous Cultures of Clostridium cellulolyticum on a Chemically Defined Medium.
- M. Desvaux, E. Guedon, and H. Petitdemange (2001)
J. Bacteriol.
183, 119-130
| Abstract »
| Full Text »
- Metabolic Modeling Identifies Key Constraints on an Engineered Glycine Betaine Synthesis Pathway in Tobacco.
- S. D. McNeil, D. Rhodes, B. L. Russell, M. L. Nuccio, Y. Shachar-Hill, and A. D. Hanson (2000)
Plant Physiology
124, 153-162
| Abstract »
| Full Text »
- Quantitative Determination of Metabolic Fluxes during Coutilization of Two Carbon Sources: Comparative Analyses with Corynebacterium glutamicum during Growth on Acetate and/or Glucose.
- V. F. Wendisch, A. A. de Graaf, H. Sahm, and B. J. Eikmanns (2000)
J. Bacteriol.
182, 3088-3096
| Abstract »
| Full Text »
- Radiotracer and Computer Modeling Evidence that Phospho-Base Methylation Is the Main Route of Choline Synthesis in Tobacco.
- S. D. McNeil, M. L. Nuccio, D. Rhodes, Y. Shachar-Hill, and A. D. Hanson (2000)
Plant Physiology
123, 371-380
| Abstract »
| Full Text »
- Metabolic Engineering of Saccharomyces cerevisiae.
- S. Ostergaard, L. Olsson, and J. Nielsen (2000)
Microbiol. Mol. Biol. Rev.
64, 34-50
| Abstract »
| Full Text »
| PDF »
- Antisense RNA Strategies for Metabolic Engineering of Clostridium acetobutylicum.
- R. P. Desai and E. T. Papoutsakis (1999)
Appl. Envir. Microbiol.
65, 936-945
| Abstract »
| Full Text »
- In Vivo Fluxes in the Ammonium-Assimilatory Pathways in Corynebacterium glutamicum Studied by 15N Nuclear Magnetic Resonance.
- M. Tesch, A. A. de Graaf, and H. Sahm (1999)
Appl. Envir. Microbiol.
65, 1099-1109
| Abstract »
| Full Text »
- Identification of Enzymes and Quantification of Metabolic Fluxes in the Wild Type and in a Recombinant Aspergillus oryzae Strain.
- H. Pedersen, M. Carlsen, and J. Nielsen (1999)
Appl. Envir. Microbiol.
65, 11-19
| Abstract »
| Full Text »
- Unidirectional Steady State Rates of Central Metabolism Enzymes Measured Simultaneously in a Living Plant Tissue.
- A. Roscher, L. Emsley, P. Raymond, and C. Roby (1998)
J. Biol. Chem.
273, 25053-25061
| Abstract »
| Full Text »
| PDF »
- Application of Biochemical Systems Theory to Metabolism in Human Red Blood Cells.
- T.-C. Ni and M. A. Savageau (1996)
J. Biol. Chem.
271, 7927-7941
| Abstract »
| Full Text »
| PDF »
- Metabolic Engineering of a Pentose Metabolism Pathway in Ethanologenic Zymomonas mobilis.
- M. Zhang, C. Eddy, K. Deanda, M. Finkelstein, and S. Picataggio (1995)
Science
267, 240-243
| Abstract »
| PDF »
- Toward a science of metabolic engineering.
- J. Bailey (1991)
Science
252, 1668-1675
| Abstract »
| PDF »
|
|