title: Emergence of robust growth laws from optimal regulation of ribosome synthesis.
abstract: Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large-scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome-wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply-driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms.
authors.affiliation: Department of Applied Mathematics, University of Waterloo, Waterloo, ON, Canada mscott@math.uwaterloo.ca.
authors.forename: Matthew
authors.initials: M
authors.lastname: Scott
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klumpp
authors.affiliation: Department of Physics and Center for Theoretical Biological Physics, University of California, San Diego La Jolla, CA, USA.
authors.forename: Eduard M
authors.initials: EM
authors.lastname: Mateescu
authors.affiliation: Department of Physics and Center for Theoretical Biological Physics, University of California, San Diego La Jolla, CA, USA Institute for Theoretical Studies, ETH Zurich, Zurich, Switzerland.
authors.forename: Terence
authors.initials: T
authors.lastname: Hwa
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000596:Amino Acids / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D008962:Models, Theoretical; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D020543:Proteome
keywords: growth control; metabolic control; phenomenological model; resource allocation; synthetic biology