Emergence of Robust Growth Laws from Optimal Regulation of Ribosome Synthesis

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2014 Aug 24

PMID 25149558

Citations 211

Authors

Matthew Scott

Stefan Klumpp

Eduard M Mateescu

Terence Hwa

Affiliations

Soon will be listed here.

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.

Citing Articles

Carbon upshift in elicits immediate initiation of proteome-wide adaptation, coinciding with growth acceleration and pyruvate dissipation switching.

van Olst B, Boeren S, Vervoort J, Kleerebezem M mBio. 2025; 16(3):e0299024.

PMID: 39976430 PMC: 11898756. DOI: 10.1128/mbio.02990-24.

Antibiotics change the population growth rate heterogeneity and morphology of bacteria.

Kals M, Kals E, Kotar J, Donald A, Mancini L, Cicuta P PLoS Pathog. 2025; 21(2):e1012924.

PMID: 39908318 PMC: 11835381. DOI: 10.1371/journal.ppat.1012924.

Soft Modes as a Predictive Framework for Low Dimensional Biological Systems across Scales.

Russo C, Husain K, Murugan A ArXiv. 2025; .

PMID: 39764393 PMC: 11702803.

Single-cell data reveal heterogeneity of investment in ribosomes across a bacterial population.

Pavlou A, Cinquemani E, Pinel C, Giordano N, Mathilde V, Mihalcescu I Nat Commun. 2025; 16(1):285.

PMID: 39746998 PMC: 11695989. DOI: 10.1038/s41467-024-55394-5.

Genome concentration limits cell growth and modulates proteome composition in .

Makela J, Papagiannakis A, Lin W, Lanz M, Glenn S, Swaffer M Elife. 2024; 13.

PMID: 39714909 PMC: 11666246. DOI: 10.7554/eLife.97465.

References

van Heeswijk W, Westerhoff H, Boogerd F . Nitrogen assimilation in Escherichia coli: putting molecular data into a systems perspective. Microbiol Mol Biol Rev. 2013; 77(4):628-95. PMC: 3973380. DOI: 10.1128/MMBR.00025-13. View

Zaslaver A, Kaplan S, Bren A, Jinich A, Mayo A, Dekel E . Invariant distribution of promoter activities in Escherichia coli. PLoS Comput Biol. 2009; 5(10):e1000545. PMC: 2758578. DOI: 10.1371/journal.pcbi.1000545. View

Keseler I, Mackie A, Peralta-Gil M, Santos-Zavaleta A, Gama-Castro S, Bonavides-Martinez C . EcoCyc: fusing model organism databases with systems biology. Nucleic Acids Res. 2012; 41(Database issue):D605-12. PMC: 3531154. DOI: 10.1093/nar/gks1027. View

Lee L, RAVEL J, SHIVE W . Multimetabolite control of a biosynthetic pathway by sequential metabolites. J Biol Chem. 1966; 241(22):5479-80. View

Murray H, Schneider D, Gourse R . Control of rRNA expression by small molecules is dynamic and nonredundant. Mol Cell. 2003; 12(1):125-34. DOI: 10.1016/s1097-2765(03)00266-1. View

Guido N, Wang X, Adalsteinsson D, McMillen D, Hasty J, Cantor C . A bottom-up approach to gene regulation. Nature. 2006; 439(7078):856-60. DOI: 10.1038/nature04473. View

Ruhlmann A, Cramer F, Englisch U . Isolation and analysis of mutated histidyl-tRNA synthetases from Escherichia coli. Biochem Biophys Res Commun. 1997; 237(1):192-201. DOI: 10.1006/bbrc.1997.7108. View

Okamoto M, Savageau M . Integrated function of a kinetic proofreading mechanism: dynamic analysis separating the effects of speed and substrate competition on accuracy. Biochemistry. 1984; 23(8):1710-5. DOI: 10.1021/bi00303a020. View

Roy H, Ling J, Irnov M, Ibba M . Post-transfer editing in vitro and in vivo by the beta subunit of phenylalanyl-tRNA synthetase. EMBO J. 2004; 23(23):4639-48. PMC: 533057. DOI: 10.1038/sj.emboj.7600474. View

10.

Wintermeyer W, Peske F, Beringer M, Gromadski K, Savelsbergh A, Rodnina M . Mechanisms of elongation on the ribosome: dynamics of a macromolecular machine. Biochem Soc Trans. 2004; 32(Pt 5):733-7. DOI: 10.1042/BST0320733. View

11.

Miller R, Stadtman E . Glutamate synthase from Escherichia coli. An iron-sulfide flavoprotein. J Biol Chem. 1972; 247(22):7407-19. View

12.

Ehrenberg M, Kurland C . Costs of accuracy determined by a maximal growth rate constraint. Q Rev Biophys. 1984; 17(1):45-82. DOI: 10.1017/s0033583500005254. View

13.

Karr J, Sanghvi J, Macklin D, Gutschow M, Jacobs J, Bolival Jr B . A whole-cell computational model predicts phenotype from genotype. Cell. 2012; 150(2):389-401. PMC: 3413483. DOI: 10.1016/j.cell.2012.05.044. View

14.

Tadmor A, Tlusty T . A coarse-grained biophysical model of E. coli and its application to perturbation of the rRNA operon copy number. PLoS Comput Biol. 2008; 4(4):e1000038. PMC: 2320978. DOI: 10.1371/journal.pcbi.1000038. View

15.

Stehlin C, Heacock 2nd D, Liu H . Chemical modification and site-directed mutagenesis of the single cysteine in motif 3 of class II Escherichia coli prolyl-tRNA synthetase. Biochemistry. 1997; 36(10):2932-8. DOI: 10.1021/bi962295s. View

16.

Jin L, Xue W, Fukayama J, Yetter J, Pickering M, Carey J . Asymmetric allosteric activation of the symmetric ArgR hexamer. J Mol Biol. 2005; 346(1):43-56. DOI: 10.1016/j.jmb.2004.11.031. View

17.

Kern D, Potier S, Lapointe J, Boulanger Y . The glutaminyl-transfer RNA synthetase of Escherichia coli. Purification, structure and function relationship. Biochim Biophys Acta. 1980; 607(1):65-80. DOI: 10.1016/0005-2787(80)90221-x. View

18.

Herring C, Raghunathan A, Honisch C, Patel T, Applebee M, Joyce A . Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale. Nat Genet. 2006; 38(12):1406-12. DOI: 10.1038/ng1906. View

19.

Schomburg I, Chang A, Hofmann O, Ebeling C, Ehrentreich F, Schomburg D . BRENDA: a resource for enzyme data and metabolic information. Trends Biochem Sci. 2002; 27(1):54-6. DOI: 10.1016/s0968-0004(01)02027-8. View

20.

Woolfolk C, Stadtman E . Regulation of glutamine synthetase. 3. Cumulative feedback inhibition of glutamine synthetase from Escherichia coli. Arch Biochem Biophys. 1967; 118(3):736-55. DOI: 10.1016/0003-9861(67)90412-2. View