Gene regulation in continuous cultures: a unified theory for bacteria and yeasts

DOI10.1007/S11538-008-9369-3MaRDI QIDQ841812zbMATH OpenOpenAlexWikidataFDO

Authors Jason T. Noel, Atul Narang

Publication date 18 September 2009

Published in Bulletin of Mathematical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/0801.1296

zbMATH Keywords

chemostatgene expressionmathematical modelmulti-substrate growth

Mathematics Subject Classification ID

Qualitative investigation and simulation of ordinary differential equation models (34C60) Probabilistic models, generic numerical methods in probability and statistics (65C20) Biochemistry, molecular biology (92C40) Ecology (92D40)

Abstract: During batch growth on mixtures of two growth-limiting substrates, microbes consume the substrates either sequentially or simultaneously. These growth patterns are manifested in all types of bacteria and yeasts. The ubiquity of these growth patterns suggests that they are driven by a universal mechanism common to all microbial species. In previous work, we showed that a minimal model accounting only for enzyme induction and dilution explains the phenotypes observed in batch cultures of various wild-type and mutant/recombinant cells. Here, we examine the extension of the minimal model to continuous cultures. We show that: (1) Several enzymatic trends, usually attributed to specific regulatory mechanisms such as catabolite repression, are completely accounted for by dilution. (2) The bifurcation diagram of the minimal model for continuous cultures, which classifies the substrate consumption pattern at any given dilution rate and feed concentrations, provides a a precise explanation for the empirically observed correlation between the growth patterns in batch and continuous cultures. (3) Numerical simulations of the model are in excellent agreement with the data. The model captures the variation of the steady state substrate concentrations, cell densities, and enzyme levels during the single- and mixed-substrate growth of bacteria and yeasts at various dilution rates and feed concentrations. (4) This variation is well-approximated by simple analytical expressions that furnish physical insights into the steady states of continuous cultures. The minimal model provides a framework for quantitating the effect of regulatory mechanisms. We illustrate this by analyzing several data sets from the literature.

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Cites work

• Bistability of the lac operon during growth of Escherichia coli on lactose and lactose + glucose
• Design principles for elementary gene circuits: Elements, methods, and examples

Cited in

(3)

• Comparative analysis of some models of gene regulation in mixed-substrate microbial growth
• Bacterial gene regulation in diauxic and non-diauxic growth
• From Staphylococcus aureus gene regulation to its pattern formation

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