Fundamental limits on the rate of bacterial growth and their influence on proteomic composition

Life on Earth, including for microbes and cold-blooded animals, often occurs in frigid environments. At frigid temperatures, nearly all intracellular processes slow down which is colloquially said to decelerate life's pace and, potentially, aging. But even for one cell, an outstanding conceptual challenge is rigorously explaining how the slowed-down intracellular processes collectively sustain a cell's life and set its pace. Here, by monitoring individual yeast cells for months at near-freezing temperatures, we show how global gene-expression dynamics and Reactive Oxygen Species (ROS) act together as the primary factors that dictate and constrain the pace at which a budding yeast's life can progresses in frigid environments. We discovered that yeast cells help each other in surviving and dividing at frigid temperatures. By investigating the underlying mechanism, involving glutathione secretion, we discovered that ROS is the primary determinant of yeast's ability to survive and divide at near-freezing temperatures. Observing days-to-months-long cell-cycle progression in individual cells revealed that ROS inhibits S-G2-M (replicative) phase while elongating G1 (growth) phase up to a temperature-dependent threshold duration, beyond which yeast cannot divide and bursts as an unsustainably large cell. We discovered that an interplay between global gene-expression speed and ROS sets the threshold G1-duration by measuring rates of genome-wide transcription and protein synthesis at frigid temperatures and then incorporating them into a mathematical model. The same interplay yields unbeatable "speed limits" for cell cycling - shortest and longest allowed doubling times - at each temperature. These results establish quantitative principles for engineering cold-tolerant microbes and reveal how frigid temperatures can fundamentally constrain microbial life and cell cycle at the systems-level.

show abstract

“…Finding quantitative "growth laws" for microbes is a goal that has attracted much attention 29,[41][42][43][44][45][46][47][48] .…”

Section: Discussionmentioning

confidence: 99%

Fundamental limits to progression of cellular life in frigid environments

Trip

Maire

Youk

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…An important implication from the agreement between observed stoichiometries and our predictions is that most tlFs are co-limiting for growth. Previous models have focused on expression optimization for the full translation sector, ribosomes (Scott et al, 2010(Scott et al, , 2014Belliveau et al, 2021), and the abundant elongation factors EF-Tu (Ehrenberg and Kurland, 1984;Klumpp et al, 2013). In a recent study, Hu and colleagues considered additional RNA components and EF-Ts in their optimization procedure (Hu et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

First-principles model of optimal translation factors stoichiometry

Lalanne

2021

eLife

View full text Add to dashboard Cite

Enzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here we report a biophysical, first-principles model of growth optimization for core mRNA translation, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that predictions from maximization of ribosome usage in a parsimonious flux model constrained by proteome allocation agree with the conserved ratios of translation factors. The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion constants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry.

show abstract

“…Restoration of the native error rate would require reducing k p and/or increasing other rate constants. On the one hand, reducing k p directly slows down the speed of protein synthesis and eventually the speed of cell growth, especially since translation is suggested as a rate-governing process in bacterial growth [45]. If all the other rate constants remain invariant, k p needs to be decreased 700-fold to recover the native error rate.…”

Section: Error-cost Trade-off In Real Biological Networkmentioning

confidence: 99%

The energy cost and optimal design of networks for biological discrimination

Kolomeisky

Igoshin

2022

J. R. Soc. Interface.

View full text Add to dashboard Cite

Many biological processes discriminate between correct and incorrect substrates through the kinetic proofreading mechanism that enables lower error at the cost of higher energy dissipation. Elucidating physico-chemical constraints for global minimization of dissipation and error is important for understanding enzyme evolution. Here, we identify theoretically a fundamental error–cost bound that tightly constrains the performance of proofreading networks under any parameter variations preserving the rate discrimination between substrates. The bound is kinetically controlled, i.e. completely determined by the difference between the transition state energies on the underlying free energy landscape. The importance of the bound is analysed for three biological processes. DNA replication by T7 DNA polymerase is shown to be nearly optimized, i.e. its kinetic parameters place it in the immediate proximity of the error–cost bound. The isoleucyl-tRNA synthetase (IleRS) of E. coli also operates close to the bound, but further optimization is prevented by the need for reaction speed. In contrast, E. coli ribosome operates in a high-dissipation regime, potentially in order to speed up protein production. Together, these findings establish a fundamental error–dissipation relation in biological proofreading networks and provide a theoretical framework for studying error–dissipation trade-off in other systems with biological discrimination.

show abstract

Fundamental limits on the rate of bacterial growth and their influence on proteomic composition

Cited by 74 publications

References 148 publications

Fundamental limits to progression of cellular life in frigid environments

Fundamental limits to progression of cellular life in frigid environments

First-principles model of optimal translation factors stoichiometry

The energy cost and optimal design of networks for biological discrimination

Contact Info

Product

Resources

About