DMCA
Regulation of Gene Expression in Flux Balance Models of Metabolism (2001)
| Venue: | J. Theor. Biol |
| Citations: | 59 - 7 self |
BibTeX
@ARTICLE{Schilling01regulationof,
author = {Christophe H. Schilling and Bernhard Palsson},
title = {Regulation of Gene Expression in Flux Balance Models of Metabolism},
journal = {J. Theor. Biol},
year = {2001},
volume = {213},
pages = {73--88}
}
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Abstract
Genome-scale metabolic networks can now be reconstructed based on annotated genomic data augmented with biochemical and physiological information about the organism. Mathematical analysis can be performed to assess the capabilities of these reconstructed networks. The constraints-based framework, with #ux balance analysis (FBA), has been used successfully to predict time course of growth and by-product secretion, e!ects of mutation and knock-outs, and gene expression pro"les. However, FBA leads to incorrect predictions in situations where regulatory e!ects are a dominant in#uence on the behavior of the organism. Thus, there is a need to include regulatory events within FBA to broaden its scope and predictive capabilities. Here we represent transcriptional regulatory events as time-dependent constraints on the capabilities of a reconstructed metabolic network to further constrain the space of possible network functions. Using a simpli"ed metabolic/regulatory network, growth is simulated under various conditions to illustrate systemic e!ects such as catabolite repression, the aerobic/anaerobic diauxic shift and amino acid biosynthesis pathway repression. The incorporation of transcriptional regulatory events in FBA enables us to interpret, analyse and predict the e!ects of transcriptional regulation on cellular metabolism at the systemic level. � 2001 Academic Press
Keyphrases
gene expression flux balance model transcriptional regulatory event constraints-based framework predictive capability cellular metabolism catabolite repression time-dependent constraint metabolic regulatory network annotated genomic data by-product secretion aerobic anaerobic diauxic shift simpli quot ux balance analysis genome-scale metabolic network regulatory ect academic press systemic level metabolic network transcriptional regulation mathematical analysis possible network function regulatory event systemic ect various condition physiological information time course amino acid biosynthesis pathway repression
