title: Constrained Allocation Flux Balance Analysis.
abstract: New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints to extend and complement Flux Balance Analysis. We introduce here Constrained Allocation Flux Balance Analysis, CAFBA, in which the biosynthetic costs associated to growth are accounted for in an effective way through a single additional genome-wide constraint. Its roots lie in the experimentally observed pattern of proteome allocation for metabolic functions, allowing to bridge regulation and metabolism in a transparent way under the principle of growth-rate maximization. We provide a simple method to solve CAFBA efficiently and propose an "ensemble averaging" procedure to account for unknown protein costs. Applying this approach to modeling E. coli metabolism, we find that, as the growth rate increases, CAFBA solutions cross over from respiratory, growth-yield maximizing states (preferred at slow growth) to fermentative states with carbon overflow (preferred at fast growth). In addition, CAFBA allows for quantitatively accurate predictions on the rate of acetate excretion and growth yield based on only 3 parameters determined by empirical growth laws.
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.|Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, Madrid, Spain.|Department of Physics, University of California at San Diego, La Jolla, California, United States of America.
authors.forename: Matteo
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Physics, University of California at San Diego, La Jolla, California, United States of America.|Institute for Theoretical Studies, ETH Zurich, Switzerland.
authors.forename: Terence
authors.initials: T
authors.lastname: Hwa
authors.affiliation: GQE - Le Moulon, INRA, Univ. Paris-Sud, CNRS, AgroParisTech, Université Paris-Saclay, Gif-sur-Yvette, France.
authors.forename: Olivier C
authors.initials: OC
authors.lastname: Martin
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.|Soft and Living Matter Lab, Istituto di Nanotecnologia (CNR-NANOTEC), Consiglio Nazionale delle Ricerche, Rome, Italy.|Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.|Human Genetics Foundation, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Martino
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.|Soft and Living Matter Lab, Istituto di Nanotecnologia (CNR-NANOTEC), Consiglio Nazionale delle Ricerche, Rome, Italy.|INFN, Sezione di Roma 1, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Marinari
mesh_terms: D000085:Acetates / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D003198:Computer Simulation; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D064688:Metabolic Flux Analysis / Q000379:methods*; D055442:Metabolome / Q000502:physiology; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000085:Acetates; D029968:Escherichia coli Proteins; D020543:Proteome