Decoupling of global metabolic flux and proteome partitioning in bacteria
Abstract
Bacteria regulate homeostatic growth by adjusting proteome composition. In Escherichia coli , this coordination is mediated by guanosine tetraphosphate and pentaphosphate, collectively termed (p)ppGpp, which couple amino acid supply with ribsosome production. We identified a distinct architecture in Bacillus subtilis , in which guanosine triphosphate (GTP), not (p)ppGpp, controls proteome allocation. Translational inhibition resulted in GTP depletion and suppressed amino acid biosynthesis through feedback inhibition without altering ribosome abundance, establishing a regulated decoupling between total amino acid flux and proteome composition, with flux deviating from proteome-based predictions. By artificially adjusting GTP concentrations, we recoupled flux and proteome, restoring growth to maximal amounts. The regulated suboptimality enables a trade-off to balance growth and stress resilience. Similar GTP-based strategies were present in other Firmicute species, indicating possible evolutionary conservation. Proteome composition and metabolic flux have distinct regulatory layers in some bacteria.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (18)
Ryan Thiermann
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Jin Yang
Aniket Zodage
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Fukang She
Department of Bacteriology, University of Wisconsin–Madison, Madison, WI, USA.
Danny K. Fung
Department of Bacteriology, University of Wisconsin–Madison, Madison, WI, USA.
Taylor Rytlewski
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Farshad Abdollah-Nia
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Fangzhou Xiao
Department of Physics, University of California San Diego, La Jolla, CA, USA.
John T. Sauls
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Sarah Cox
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Zulfar Ghulam-Jelani
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Victoria Castillo
Department of Physics, University of California San Diego, La Jolla, CA, USA.
Quinn A. Paulsen
Department of Bacteriology, University of Wisconsin–Madison, Madison, WI, USA.
David M. Stevenson
Department of Bacteriology, University of Wisconsin–Madison, Madison, WI, USA.
Daniel Amador-Noguez
Department of Bacteriology, University of Wisconsin–Madison, Madison, WI, USA.
James R. Williamson
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Jue D. Wang
Department of Bacteriology, University of Wisconsin–Madison, Madison, WI, USA.
Suckjoon Jun
Department of Physics, University of California San Diego, La Jolla, CA, USA.