Quantitative prediction of genome-wide resource allocation in bacteria.
Predicting resource allocation between cell processes is the primary step towards decoding the evolutionary constraints governing bacterial growth under various conditions. Quantitative prediction at genome-scale remains a computational challenge as current methods are limited by the tractability of the problem or by simplifying hypotheses. Here, we show that the constraint-based modeling method Resource Balance Analysis (RBA), calibrated using genome-wide absolute protein quantification data, accurately predicts resource allocation in the model bacterium Bacillus subtilis for a wide range of growth conditions. The regulation of most cellular processes is consistent with the objective of growth rate maximization except for a few suboptimal processes which likely integrate more complex objectives such as coping with stressful conditions and survival. As a proof of principle by using simulations, we illustrated how calibrated RBA could aid rational design of strains for maximizing protein production, offering new opportunities to investigate design principles in prokaryotes and to exploit them for biotechnological applications.
INRA, UR1404, MaIAGE, F-78350 Jouy-en-Josas, France.
Anne
A
Goelzer
Institute for Microbiology, Ernst-Moritz-Arndt University Greifswald, D-17489 Greifswald, Germany.
Jan
J
Muntel
Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
Victor
V
Chubukov
INRA, UMR Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech,UMR Micalis, F-78350 Jouy-en-Josas, France.
Matthieu
M
Jules
INRA, UMR Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech,UMR Micalis, F-78350 Jouy-en-Josas, France.
Eric
E
Prestel
Institute for Microbiology, Ernst-Moritz-Arndt University Greifswald, D-17489 Greifswald, Germany.
Rolf
R
Nölker
INRA, UR1404, MaIAGE, F-78350 Jouy-en-Josas, France.
Mahendra
M
Mariadassou
INRA, UMR Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech,UMR Micalis, F-78350 Jouy-en-Josas, France.
Stéphane
S
Aymerich
Institute for Microbiology, Ernst-Moritz-Arndt University Greifswald, D-17489 Greifswald, Germany.
Michael
M
Hecker
INRA, UMR Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech,UMR Micalis, F-78350 Jouy-en-Josas, France.
Philippe
P
Noirot
Institute for Microbiology, Ernst-Moritz-Arndt University Greifswald, D-17489 Greifswald, Germany.
Dörte
D
Becher
INRA, UR1404, MaIAGE, F-78350 Jouy-en-Josas, France. Electronic address: Vincent.Fromion@jouy.inra.fr.
Vincent
V
Fromion
D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism*; D003198:Computer Simulation; D016680:Genome, Bacterial / Q000235:genetics*; D060847:Metabolic Engineering / Q000379:methods; D040841:Resource Allocation
Constraint-based modeling; Resource allocation; Strain design; Systems biology