Decoupling of global metabolic flux and proteome partitioning in bacteria
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.
Authors
- John T. Sauls
- Danny K. Fung (ORCID: https://orcid.org/0000-0003-4002-7227)
- Daniel Amador‐Noguez (ORCID: https://orcid.org/0000-0002-3568-3070)
- Aniket Zodage (ORCID: https://orcid.org/0000-0001-5044-0731)
- Fukang She (ORCID: https://orcid.org/0009-0008-8633-252X)
- Jue D. Wang (ORCID: https://orcid.org/0000-0003-1503-170X)
- Fangzhou Xiao (ORCID: https://orcid.org/0000-0002-5001-5644)
- James R. Williamson (ORCID: https://orcid.org/0000-0002-8772-468X)
- Zulfar Ghulam-Jelani
- Jin Yang (ORCID: https://orcid.org/0000-0003-3442-5608)
- Ryan Thiermann (ORCID: https://orcid.org/0000-0002-0348-4181)
- Suckjoon Jun (ORCID: https://orcid.org/0000-0002-0139-4297)
- Farshad Abdollah-Nia (ORCID: https://orcid.org/0000-0002-5360-0136)
- David M. Stevenson
- Victoria del Castillo
- Quinn A. Paulsen (ORCID: https://orcid.org/0009-0004-4865-502X)
- Sarah Cox
- Taylor Rytlewski
Institutions
- Scripps Research Institute (US)
- Howard Hughes Medical Institute (US)
- University of Wisconsin–Madison (US)
- Westlake University (CN)
- University of California San Diego (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Science
- Published
- 2026-06-18
- DOI
- https://doi.org/10.1126/science.aeb6410
- Primary Topic
- Bacterial Genetics and Biotechnology
- Type
- article
- Field-Weighted Citation Impact
- 0.00