UBI seminar
 Date & Time:November. 25th, 2024 (Mon), 15:00-16:30
 Place: 1st Build. of Science, room 207 (Hongo campus, U. Tokyo)
 Speaker: Prof. Suckjoon Jun (UCSD)
 Title:Decoupling of global metabolic flux and proteome partitioning in bacteria

Abstract: Many exponentially multiplying bacteria control growth via proteome partitioning, with (p)ppGpp as the master regulator that couples amino acid supply with protein synthesis. We uncover a fundamentally different mechanism in Bacillus subtilis, where GTP, rather than (p)ppGpp, is the primary regulator of proteome allocation. This mechanism results in a state of induced overcapacity by allosterically suppressing global amino acid flux upon translational inhibition, while proteome allocation remains invariant. This invariance leads to a striking decoupling of amino acid flux from the proteome, and enables fast growth recovery when the inhibition is removed. Using GTP-tunable mutants, we exploit this mechanism to recouple flux and proteome under translational inhibition and accelerate growth rate in a manner unattainable in Escherichia coli. Proteomics data further reveals the upregulation of many stress-adaptation proteins upon GTP reduction. Based on these observations, we show that the wild-type GTP level maximizes both growth and survivability in B. subtilis. Bioinformatic analysis suggests that the GTP-centric mechanisms are widespread in bacteria. These findings challenge the growth rate-optimizing paradigm of cellular resource allocation in microbiology, highlighting a broader diversity of physiological strategies and evolutionary adaptations among bacterial species.