Emergence of robust growth laws from optimal regulation of ribosome synthesis

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.

• Publication year

  2014

• Venue

  Molecular Systems Biology

• Publication date

  2014-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.15252/msb.20145379PMID 25149558PMCID 4299513
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources.

  2014influential reference
• Bacterial growth: global effects on gene expression, growth feedback and proteome partition.

  2014cited by this paper
• Molecular crowding limits translation and cell growth

  2013influential reference
• Coordination of bacterial proteome with metabolism by cyclic AMP signalling

  2013influential reference
• From essential to persistent genes: a functional approach to constructing synthetic life

  2013cited by this paper
• Heterogeneity in protein expression induces metabolic variability in a modeled Escherichia coli population

  2013cited by this paper
• Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

  2013cited by this paper
• The Innate Growth Bistability and Fitness Landscapes of Antibiotic-Resistant Bacteria

  2013influential reference
• Optimal control of gene expression for fast proteome adaptation to environmental change

  2013influential reference
• Exploring the allosteric mechanism of dihydrodipicolinate synthase by reverse engineering of the allosteric inhibitor binding sites and its application for lysine production

  2013cited by this paper
• What is the total number of protein molecules per cell volume? A call to rethink some published values

  2013influential reference
• A whole-cell computational model predicts phenotype from genotype.

  2012cited by this paper
• Need-based activation of ammonium uptake in Escherichia coli

  2012cited by this paper
• EcoCyc: fusing model organism databases with systems biology

  2012cited by this paper
• Functioning of a metabolic flux sensor in Escherichia coli

  2012cited by this paper
• Bacterial growth laws and their applications.

  2011influential reference
• ppGpp is the major source of growth rate control in E. coli.

  2011cited by this paper
• Five hard truths for synthetic biology

  2010cited by this paper
• Interdependence of Cell Growth and Gene Expression: Origins and Consequences

  2010influential reference
• Bacterial adaptation through distributed sensing of metabolic fluxes

  2010cited by this paper
• Shifts in growth strategies reflect tradeoffs in cellular economics

  2009cited by this paper
• Invariant Distribution of Promoter Activities in Escherichia coli

  2009cited by this paper
• Nonoptimal microbial response to antibiotics underlies suppressive drug interactions.

  2009cited by this paper
• Absolute Metabolite Concentrations and Implied Enzyme Active Site Occupancy in Escherichia coli

  2009cited by this paper
• Growth rate-dependent global effects on gene expression in bacteria.

  2009influential reference
• A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number

  2008cited by this paper
• Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale

  2006cited by this paper
• Purification and Characterization

  2006cited by this paper
• Fast, cheap and somewhat in control

  2006cited by this paper
• The Elongation Cycle

  2006cited by this paper
• A bottom-up approach to gene regulation

  2006cited by this paper
• Asymmetric allosteric activation of the symmetric ArgR hexamer.

  2005cited by this paper
• Recognition and selection of tRNA in translation

  2005cited by this paper
• An aminoacyl-tRNA synthetase with a defunct editing site.

  2005cited by this paper
• Near-critical behavior of aminoacyl-tRNA pools in E. coli at rate-limiting supply of amino acids.

  2005cited by this paper
• Functional group recognition at the aminoacylation and editing sites of E. coli valyl-tRNA synthetase.

  2004cited by this paper
• Discrimination of cognate and noncognate substrates at the active site of class II lysyl-tRNA synthetase.

  2004cited by this paper
• Mechanisms of elongation on the ribosome: dynamics of a macromolecular machine.

  2004cited by this paper
• Near-critical behavior of aminoacyl-tRNA pools at rate limiting supply of several types of amino acids in E. coli.

  2004cited by this paper
• Post‐transfer editing in vitro and in vivo by the β subunit of phenylalanyl‐tRNA synthetase

  2004cited by this paper
• Protein synthesis and ribosome structure : translating the genome

  2004cited by this paper
• rRNA transcription in Escherichia coli.

  2004cited by this paper
• Discrimination of cognate and noncognate substrates at the active site of class I lysyl-tRNA synthetase.

  2004cited by this paper
• Control of rRNA expression by small molecules is dynamic and nonredundant.

  2003cited by this paper
• The Asparagine Synthetase of Escherichia coli ON MECHANISM*

  2003cited by this paper
• BRENDA: a resource for enzyme data and metabolic information.

  2002cited by this paper
• An engineered Escherichia coli tyrosyl–tRNA synthetase for site-specific incorporation of an unnatural amino acid into proteins in eukaryotic translation and its application in a wheat germ cell-free system

  2002cited by this paper
• Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway.

  2002cited by this paper
• A dispensable peptide from Acidithiobacillus ferrooxidans tryptophanyl‐tRNA synthetase affects tRNA binding

  2002cited by this paper
• Charging levels of four tRNA species in Escherichia coli Rel(+) and Rel(-) strains during amino acid starvation: a simple model for the effect of ppGpp on translational accuracy.

  2001cited by this paper
• Initiation Factor and Ribosome Levels

  2001cited by this paper
• Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase

  2000cited by this paper
• From molecular to modular cell biology

  1999cited by this paper
• The identity determinants required for the discrimination between tRNAGlu and tRNAAsp by glutamyl-tRNA synthetase from Escherichia coli.

  1999cited by this paper
• Modulation of Chemical Composition and Other Parameters of the Cell by Growth Rate

  1999cited by this paper
• The Physiology and Biochemistry of Prokaryotes

  1999cited by this paper
• Resources

  1998cited by this paper
• Fast recycling of Escherichia coli ribosomes requires both ribosome recycling factor (RRF) and release factor RF3

  1997cited by this paper
• Isolation and analysis of mutated histidyl-tRNA synthetases from Escherichia coli.

  1997cited by this paper
• Chemical modification and site-directed mutagenesis of the single cysteine in motif 3 of class II Escherichia coli prolyl-tRNA synthetase.

  1997cited by this paper
• Characterization of a thermosensitive Escherichia coli aspartyl-tRNA synthetase mutant

  1997cited by this paper
• Escherichia coli and Salmonella.

  1996cited by this paper
• Control of rRNA transcription in Escherichia coli.

  1995cited by this paper
• Seryl-tRNA synthetase from Escherichia coli: implication of its N-terminal domain in aminoacylation activity and specificity.

  1994cited by this paper
• The origins and meaning of the Schaechter-Maaløe-Kjeldgaard experiments

  1993cited by this paper
• Amino acid substitutions at position 73 in motif 2 of Escherichia coli alanyl-tRNA synthetase.

  1993cited by this paper
• Asparaginyl‐tRNA synthetase from the Escherichia coli temperature‐sensitive strain HO202 A proline replacement in motif 2 is responsible for a large increase in K m for asparagine and ATP

  1992cited by this paper
• Kinetic studies on chorismate mutase-prephenate dehydrogenase from Escherichia coli: models for the feedback inhibition of prephenate dehydrogenase by L-tyrosine.

  1991cited by this paper
• GROWTH INHIBITION OF

  1991cited by this paper
• Physiology of the bacterial cell : a molecular approach

  1990cited by this paper
• Structure-function relationship of arginyl-tRNA synthetase from Escherichia coli: isolation and characterization of the argS mutation MA5002.

  1990cited by this paper
• Escherichia Coli and Salmonella: Typhimurium Cellular and Molecular Biology

  1987cited by this paper
• Independence of buoyant cell density and growth rate in Escherichia coli

  1984cited by this paper
• Integrated function of a kinetic proofreading mechanism: dynamic analysis separating the effects of speed and substrate competition on accuracy.

  1984cited by this paper
• Regulation of the synthesis of ribosomes and ribosomal components.

  1984cited by this paper
• Costs of accuracy determined by a maximal growth rate constraint

  1984cited by this paper
• Initiation factor and ribosome levels are coordinately controlled in Escherichia coli growing at different rates.

  1983cited by this paper
• Biological Regulation and Development

  1982cited by this paper
• Regulation of aromatic amino acid transport by tRNA: role of 2-methylthio-N6-(delta2-isopentenyl)-adenosine.

  1981cited by this paper
• Regulation of glutamine synthetase.

  1980cited by this paper
• The glutaminyl-transfer RNA synthetase of Escherichia coli. Purification, structure and function relationship.

  1980cited by this paper
• Regulation of ribosomal protein synthesis in Escherichia coli by selective mRNA inactivation.

  1979cited by this paper
• Growth inhibition as a consequence of antagonism between related amino acids: effect of valine in Escherichia coli K-12

  1979cited by this paper
• Regulation of the Protein-Synthesizing Machinery—Ribosomes, tRNA, Factors, and So On

  1979influential reference
• Patterns of protein synthesis in E. coli: a catalog of the amount of 140 individual proteins at different growth rates.

  1978cited by this paper
• Biochemical systems analysis: A study of function and design in molecular biology

  1978cited by this paper
• Regulation of aromatic amino acid transport systems in Escherichia coli K-12

  1977cited by this paper
• Regulation of amino acid transport in Escherichia coli by transcription termination factor rho

  1977cited by this paper
• Purification and characterization of a mutant ATP phosphoribosyltransferase hypersensitive to histidine feedback inhibition.

  1977cited by this paper
• Chemical measurement of steady-state levels of ten aminoacyl-transfer ribonucleic acid synthetases in Escherichia coli

  1977cited by this paper
• The mechanism of end product inhibition of serine biosynthesis. V. Mechanism of serim inhibition of phosphoglycerate dehydrogenases.

  1975cited by this paper
• A new method for the isolation of methionyl transfer RNA synthetase mutants from Escherichia coli.

  1975cited by this paper
• Optimal design of feedback control by inhibition

  1975cited by this paper
• [Protein synthesis].

  1974cited by this paper
• ESCHERICHIA COLI K-12*

  1973influential reference
• Chorismate mutase-prephenate dehydratase from Escherichia coli K-12. II. Kinetic properties.

  1972cited by this paper
• Glutamate synthase from Escherichia coli. An iron-sulfide flavoprotein.

  1972cited by this paper
• The asparagine synthetase of Escherichia coli. II. Studies on mechanism.

  1969cited by this paper
• The asparagine synthetase of Escherhic coli. I. Biosynthetic role of the enzyme, purification, and characterization of the reaction products.

  1969cited by this paper
• The mechanism of end product inhibition of serine biosynthesis. I. Purification and kinetics of phosphoglycerate dehydrogenase.

  1968cited by this paper

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  2026cites this paper
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