Mapping high-growth phenotypes in the flux space of microbial metabolism.
Experimental and empirical observations on cell metabolism cannot be understood as a whole without their integration into a consistent systematic framework. However, the characterization of metabolic flux phenotypes is typically reduced to the study of a single optimal state, such as maximum biomass yield that is by far the most common assumption. Here, we confront optimal growth solutions to the whole set of feasible flux phenotypes (FFPs), which provides a benchmark to assess the likelihood of optimal and high-growth states and their agreement with experimental results. In addition, FFP maps are able to uncover metabolic behaviours, such as aerobic fermentation accompanying exponential growth on sugars at nutrient excess conditions, that are unreachable using standard models based on optimality principles. The information content of the full FFP space provides us with a map to explore and evaluate metabolic behaviour and capabilities, and so it opens new avenues for biotechnological and biomedical applications.
Departament de Química Física, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
Oriol
O
Güell
Departament d'Enginyeria Química, Universitat Rovira i Virgili, 43007 Tarragona, Spain.
Francesco Alessandro
FA
Massucci
Centre de Recerca Matemàtica, Edifici C, Campus Bellaterra, Bellaterra, 08193 Barcelona, Spain Departament de Matemàtiques, Universitat Autònoma de Barcelona, Edifici C, Campus Bellaterra, Bellaterra, 08193 Barcelona, Spain.
Francesc
http://orcid.org/0000-0003-4938-2452
F
Font-Clos
Departament de Química Física, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
Francesc
F
Sagués
Departament de Física, Fonamental, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain marian.serrano@ub.edu.
M Ángeles
MÁ
Serrano
D001419:Bacteria / Q000378:metabolism*; D018533:Biomass; D059013:Microbial Consortia / Q000502:physiology*; D008954:Models, Biological
cellular metabolism; flux balance analysis; flux space