Regulation of gene expression in flux balance models of metabolism

Covert, MW Schilling, CH Palsson, B

Mw. Covert et al., Regulation of gene expression in flux balance models of metabolism, J THEOR BIO, 213(1), 2001, pp. 73-88

58

INGLESE

Article

Multidisciplinary

JOURNAL OF THEORETICAL BIOLOGY

0022-5193 → ACNP

213

1

2001

73 - 88

ISI

0022-5193(20011107)213:1<73:ROGEIF>2.0.ZU;2-A

Genome-scale metabolic networks can now be reconstructed based on annotated genomic data augmented with biochemical and physiological information abou t the organism. Mathematical analysis can be performed to assess the capabi lities of these reconstructed networks. The constraints-based framework, wi th flux balance analysis (FBA), has been used successfully to predict time course of growth and by-product secretion, effects of mutation and knock-ou ts, and gene expression profiles. However, FBA leads to incorrect predictio ns in situations where regulatory effects are a dominant influence on the b ehavior of the organism. Thus, there is a need to include regulatory events within FBA to broaden its scope and predictive capabilities. Here we repre sent 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 simplified metabolic/regulato ry network, growth is simulated under various conditions to illustrate syst emic effects such as catabolite repression, the aerobic/anaerobic diauxic s hift and amino acid biosynthesis pathway repression. The incorporation of t ranscriptional regulatory events in FBA enables us to interpret, analyse an d predict the effects of transcriptional regulation on cellular metabolism at the systemic level. (C) 2001 Academic Press.