• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biophysjLink to Publisher's site
Biophys J. Sep 2002; 83(3): 1331–1340.
PMCID: PMC1302231

Dynamic flux balance analysis of diauxic growth in Escherichia coli.


Flux Balance Analysis (FBA) has been used in the past to analyze microbial metabolic networks. Typically, FBA is used to study the metabolic flux at a particular steady state of the system. However, there are many situations where the reprogramming of the metabolic network is important. Therefore, the dynamics of these metabolic networks have to be studied. In this paper, we have extended FBA to account for dynamics and present two different formulations for dynamic FBA. These two approaches were used in the analysis of diauxic growth in Escherichia coli. Dynamic FBA was used to simulate the batch growth of E. coli on glucose, and the predictions were found to qualitatively match experimental data. The dynamic FBA formalism was also used to study the sensitivity to the objective function. It was found that an instantaneous objective function resulted in better predictions than a terminal-type objective function. The constraints that govern the growth at different phases in the batch culture were also identified. Therefore, dynamic FBA provides a framework for analyzing the transience of metabolism due to metabolic reprogramming and for obtaining insights for the design of metabolic networks.

Full Text

The Full Text of this article is available as a PDF (263K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cohen BA, Mitra RD, Hughes JD, Church GM. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat Genet. 2000 Oct;26(2):183–186. [PubMed]
  • de Saizieu A, Certa U, Warrington J, Gray C, Keck W, Mous J. Bacterial transcript imaging by hybridization of total RNA to oligonucleotide arrays. Nat Biotechnol. 1998 Jan;16(1):45–48. [PubMed]
  • Edwards JS, Ibarra RU, Palsson BO. In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat Biotechnol. 2001 Feb;19(2):125–130. [PubMed]
  • Giuseppin ML, van Riel NA. Metabolic modeling of Saccharomyces cerevisiae using the optimal control of homeostasis: a cybernetic model definition. Metab Eng. 2000 Jan;2(1):14–33. [PubMed]
  • Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, Bumgarner R, Goodlett DR, Aebersold R, Hood L. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science. 2001 May 4;292(5518):929–934. [PubMed]
  • Kirkpatrick C, Maurer LM, Oyelakin NE, Yoncheva YN, Maurer R, Slonczewski JL. Acetate and formate stress: opposite responses in the proteome of Escherichia coli. J Bacteriol. 2001 Nov;183(21):6466–6477. [PMC free article] [PubMed]
  • Lendenmann U, Egli T. Kinetic models for the growth of Escherichia coli with mixtures of sugars under carbon-limited conditions. Biotechnol Bioeng. 1998 Jul 5;59(1):99–107. [PubMed]
  • Oh MK, Liao JC. Gene expression profiling by DNA microarrays and metabolic fluxes in Escherichia coli. Biotechnol Prog. 2000 Mar-Apr;16(2):278–286. [PubMed]
  • Schilling CH, Letscher D, Palsson BO. Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective. J Theor Biol. 2000 Apr 7;203(3):229–248. [PubMed]
  • Schilling CH, Edwards JS, Letscher D, Palsson BØ Combining pathway analysis with flux balance analysis for the comprehensive study of metabolic systems. Biotechnol Bioeng. 2000;71(4):286–306. [PubMed]
  • Selinger DW, Cheung KJ, Mei R, Johansson EM, Richmond CS, Blattner FR, Lockhart DJ, Church GM. RNA expression analysis using a 30 base pair resolution Escherichia coli genome array. Nat Biotechnol. 2000 Dec;18(12):1262–1268. [PubMed]
  • Stephanopoulos G. Metabolic fluxes and metabolic engineering. Metab Eng. 1999 Jan;1(1):1–11. [PubMed]
  • Tao H, Bausch C, Richmond C, Blattner FR, Conway T. Functional genomics: expression analysis of Escherichia coli growing on minimal and rich media. J Bacteriol. 1999 Oct;181(20):6425–6440. [PMC free article] [PubMed]
  • Tao H, Gonzalez R, Martinez A, Rodriguez M, Ingram LO, Preston JF, Shanmugam KT. Engineering a homo-ethanol pathway in Escherichia coli: increased glycolytic flux and levels of expression of glycolytic genes during xylose fermentation. J Bacteriol. 2001 May;183(10):2979–2988. [PMC free article] [PubMed]
  • Tavazoie S, Hughes JD, Campbell MJ, Cho RJ, Church GM. Systematic determination of genetic network architecture. Nat Genet. 1999 Jul;22(3):281–285. [PubMed]
  • Varma A, Palsson BO. Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl Environ Microbiol. 1994 Oct;60(10):3724–3731. [PMC free article] [PubMed]
  • Varma A, Boesch BW, Palsson BO. Stoichiometric interpretation of Escherichia coli glucose catabolism under various oxygenation rates. Appl Environ Microbiol. 1993 Aug;59(8):2465–2473. [PMC free article] [PubMed]
  • Varner JD. Large-scale prediction of phenotype: concept. Biotechnol Bioeng. 2000 Sep 20;69(6):664–678. [PubMed]
  • Varner J, Ramkrishna D. Metabolic engineering from a cybernetic perspective. 1. Theoretical preliminaries . Biotechnol Prog. 1999 May;15(3):407–425. [PubMed]
  • Wei Y, Lee JM, Richmond C, Blattner FR, Rafalski JA, LaRossa RA. High-density microarray-mediated gene expression profiling of Escherichia coli. J Bacteriol. 2001 Jan;183(2):545–556. [PMC free article] [PubMed]
  • Wong P, Gladney S, Keasling JD. Mathematical model of the lac operon: inducer exclusion, catabolite repression, and diauxic growth on glucose and lactose. Biotechnol Prog. 1997 Mar-Apr;13(2):132–143. [PubMed]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...