2,001 research outputs found
Nutrient levels and trade-offs control diversity in a serial dilution ecosystem
Microbial communities feature an immense diversity of species and this
diversity is linked with outcomes ranging from ecosystem stability to medical
prognoses. Yet the mechanisms underlying microbial diversity are under debate.
While simple resource-competition models don't allow for coexistence of a large
number of species, it was recently shown that metabolic trade-offs can allow
unlimited diversity. Does this diversity persist with more realistic,
intermittent nutrient supply? Here, we demonstrate theoretically that in serial
dilution culture, metabolic trade-offs allow for high diversity. When a small
amount of nutrient is supplied to each batch, the serial dilution dynamics
mimic a chemostat-like steady state. If more nutrient is supplied, diversity
depends on the amount of nutrient supplied due to an "early-bird" effect. The
interplay of this effect with different environmental factors and
diversity-supporting mechanisms leads to a variety of relationships between
nutrient supply and diversity, suggesting that real ecosystems may not obey a
universal nutrient-diversity relationship.Comment: Appendix follows main tex
Microbial inefficient substrate use through the perspective of resource allocation models
Microorganisms extract energy from substrates following strategies that may seem suboptimal at first glance. Beyond the so-called yield-rate trade-off, resource allocation models, which focus on assigning different functional roles to the limited number of enzymes that a cell can support, offer a framework to interpret the inefficient substrate use by microorganisms. We review here relevant examples of substrate conversions where a significant part of the available energy is not utilised and how resource allocation models offer a mechanistic interpretation thereof, notably for open mixed cultures. Future developments are identified, in particular, the challenge of considering metabolic flexibility towards uncertain environmental changes instead of strict fixed optimality objectives, with the final goal of increasing the prediction capabilities of resource allocation models. Finally, we highlight the relevance of resource allocation to understand and enable a promising biorefinery platform revolving around lactate, which would increase the flexibility of waste-to-chemical biorefinery schemese authors would like to acknowledge the support of the Spanish Ministry of Education (FPU14/05457) and project CONSERVAL (INTERREG V-A Spain-Portugal, POCTEP), co-financed by the ERDF (Ref: 2352). The authors belong to the Galician Competitive Research Group (ED431C2017/029) and to the CRETUS Strategic Partnership (ED431E 2018/01), both programmes are co-funded by Xunta de Galicia and ERDF (EU)S
How enzyme economy shapes metabolic fluxes
Metabolic fluxes are governed by physical and economic principles.
Stationarity constrains them to a subspace in flux space and thermodynamics
makes them lead from higher to lower chemical potentials. At the same time,
fluxes in cells represent a compromise between metabolic performance and enzyme
cost. To capture this, some flux prediction methods penalise larger fluxes by
heuristic cost terms. Economic flux analysis, in contrast, postulates a balance
between enzyme costs and metabolic benefits as a necessary condition for fluxes
to be realised by kinetic models with optimal enzyme levels. The constraints
are formulated using economic potentials, state variables that capture the
enzyme labour embodied in metabolites. Generally, fluxes must lead from lower
to higher economic potentials. This principle, which resembles thermodynamic
constraints, can complement stationarity and thermodynamic constraints in flux
analysis. Futile modes, which would be incompatible with economic potentials,
are defined algebraically and can be systematically removed from flux
distributions. Enzymes that participate in potential futile modes are likely
targets of regulation. Economic flux analysis can predict high-yield and
low-yield strategies, and captures preemptive expression, multi-objective
optimisation, and flux distributions across several cells living in symbiosis.
Inspired by labour value theories in economics, it justifies and extends the
principle of minimal fluxes and provides an intuitive framework to model the
complex interplay of fluxes, metabolic control, and enzyme costs in cells
Evolutionary coexistence in a fluctuating environment by specialization on resource level
Microbial communities in fluctuating environments, such as oceans or the human gut, contain a wealth of diversity. This diversity contributes to the stability of communities and the functions they have in their hosts and ecosystems. To improve stability and increase production of beneficial compounds, we need to understand the underlying mechanisms causing this diversity. When nutrient levels fluctuate over time, one possibly relevant mechanism is coexistence between specialists on low and specialists on high nutrient levels. The relevance of this process is supported by the observations of coexistence in the laboratory, and by simple models, which show that negative frequency dependence of two such specialists can stabilize coexistence. However, as microbial populations are often large and fast growing, they evolve rapidly. Our aim is to determine what happens when species can evolve; whether evolutionary branching can create diversity or whether evolution will destabilize coexistence. We derive an analytical expression of the invasion fitness in fluctuating environments and use adaptive dynamics techniques to find that evolutionarily stable coexistence requires a special type of trade-off between growth at low and high nutrients. We do not find support for the necessary evolutionary trade-off in data available for the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae on glucose. However, this type of data is scarce and might exist for other species or in different conditions. Moreover, we do find evidence for evolutionarily stable coexistence of the two species together. Since we find this coexistence in the scarce data that are available, we predict that specialization on resource level is a relevant mechanism for species diversity in microbial communities in fluctuating environments in natural settings
A physical model of cell metabolism
Cell metabolism is characterized by three fundamental energy demands: to sustain cell maintenance, to trigger aerobic fermentation and to achieve maximum metabolic rate. The transition to aerobic fermentation and the maximum metabolic rate are currently understood based on enzymatic cost constraints. Yet, we are lacking a theory explaining the maintenance energy demand. Here we report a physical model of cell metabolism that explains the origin of these three energy scales. Our key hypothesis is that the maintenance energy demand is rooted on the energy expended by molecular motors to fluidize the cytoplasm and counteract molecular crowding. Using this model and independent parameter estimates we make predictions for the three energy scales that are in quantitative agreement with experimental values. The model also recapitulates the dependencies of cell growth with extracellular osmolarity and temperature. This theory brings together biophysics and cell biology in a tractable model that can be applied to understand key principles of cell metabolism
An integrative approach to understanding microbial diversity: from intracellular mechanisms to community structure
Trade-offs have been put forward as essential to the generation and maintenance of diversity. However, variation in trade-offs is often determined at the molecular level, outside the scope of conventional ecological inquiry. In this study, we propose that understanding the intracellular basis for trade-offs in microbial systems can aid in predicting and interpreting patterns of diversity. First, we show how laboratory experiments and mathematical models have unveiled the hidden intracellular mechanisms underlying trade-offs key to microbial diversity: (i) metabolic and regulatory trade-offs in bacteria and yeast; (ii) life-history trade-offs in bacterial viruses. Next, we examine recent studies of marine microbes that have taken steps toward reconciling the molecular and the ecological views of trade-offs, despite the challenges in doing so in natural settings. Finally, we suggest avenues for research where mathematical modelling, experiments and studies of natural microbial communities provide a unique opportunity to integrate studies of diversity across multiple scales
Quantification and Classification of <i>E. coli </i>Proteome Utilization and Unused Protein Costs across Environments
The costs and benefits of protein expression are balanced through evolution. Expression of un-utilized protein (that have no benefits in the current environment) incurs a quantifiable fitness costs on cellular growth rates; however, the magnitude and variability of un-utilized protein expression in natural settings is unknown, largely due to the challenge in determining environment-specific proteome utilization. We address this challenge using absolute and global proteomics data combined with a recently developed genome-scale model of Escherichia coli that computes the environment-specific cost and utility of the proteome on a per gene basis. We show that nearly half of the proteome mass is unused in certain environments and accounting for the cost of this unused protein expression explains >95% of the variance in growth rates of Escherichia coli across 16 distinct environments. Furthermore, reduction in unused protein expression is shown to be a common mechanism to increase cellular growth rates in adaptive evolution experiments. Classification of the unused protein reveals that the unused protein encodes several nutrient- and stress- preparedness functions, which may convey fitness benefits in varying environments. Thus, unused protein expression is the source of large and pervasive fitness costs that may provide the benefit of hedging against environmental change
Towards a non-equilibrium thermodynamic theory of ecosystem assembly and development
Non-equilibrium thermodynamics has had a significant historic influence on the development
of theoretical ecology, even informing the very concept of an ecosystem. Much of this influence
has manifested as proposed extremal principles. These principles hold that systems will tend
to maximise certain thermodynamic quantities, subject to the other constraints they operate
under. A particularly notable extremal principle is the maximum entropy production principle
(MaxEPP); that systems maximise their rate of entropy production. However, these principles
are not robustly based in physical theory, and suffer from treating complex ecosystems in
an extremely coarse manner. To address this gap, this thesis derives a limited but physically
justified extremal principle, as well as carrying out a detailed investigation of the impact of
non-equilibrium thermodynamic constraints on the assembly of microbial communities. The extremal
principle we obtain pertains to the switching between states in simple bistable systems,
with switching paths that generate more entropy being favoured. Our detailed investigation
into microbial communities involved developing a novel thermodynamic microbial community
model, using which we found the rate of ecosystem development to be set by the availability
of free-energy. Further investigation was carried out using this model, demonstrating the way
that trade-offs emerging from fundamental thermodynamic constraints impact the dynamics of
assembling microbial communities. Taken together our results demonstrate that theory can be
developed from non-equilibrium thermodynamics, that is both ecologically relevant and physically
well grounded. We find that broad extremal principles are unlikely to be obtained, absent
significant advances in the field of stochastic thermodynamics, limiting their applicability to
ecology. However, we find that detailed consideration of the non-equilibrium thermodynamic
mechanisms that impact microbial communities can broaden our understanding of their assembly
and functioning.Open Acces
Survival of the cheapest: How proteome cost minimization drives evolution
Darwin's theory of evolution emphasized that positive selection of functional
proficiency provides the fitness that ultimately determines the structure of
life, a view that has dominated biochemical thinking of enzymes as perfectly
optimized for their specific functions. The 20th-century modern synthesis,
structural biology, and the central dogma explained the machinery of evolution,
and nearly neutral theory explained how selection competes with random fixation
dynamics that produce molecular clocks essential e.g. for dating evolutionary
histories. However, the quantitative proteomics revealed that fitness effects
not related to functional proficiency play much larger roles on long
evolutionary time scales than previously thought, with particular evidence that
some universal biophysical selection pressures act via protein expression
levels. This paper first summarizes recent progress in the 21st century towards
recovering this universal selection pressure. Then, the paper argues that
proteome cost minimization is the dominant, underlying "non-function" selection
pressure controlling most of the evolution of already functionally adapted
living systems. A theory of proteome cost minimization is described and argued
to have consequences for understanding evolutionary trade-offs, aging, cancer,
and neurodegenerative protein-misfolding diseases
Ratio of electron donor to acceptor influences metabolic specialization and denitrification dynamics in Pseudomonas aeruginosa in a mixed carbon medium
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Zhang, I. H., Mullen, S., Ciccarese, D., Dumit, D., Martocello, D. E., Toyofuku, M., Nomura, N., Smriga, S., & Babbin, A. R. Ratio of electron donor to acceptor influences metabolic specialization and denitrification dynamics in Pseudomonas aeruginosa in a mixed carbon medium. Frontiers in Microbiology, 12, (2021): 711073, https://doi.org/10.3389/fmicb.2021.711073.Denitrifying microbes sequentially reduce nitrate (NO3–) to nitrite (NO2–), NO, N2O, and N2 through enzymes encoded by nar, nir, nor, and nos. Some denitrifiers maintain the whole four-gene pathway, but others possess partial pathways. Partial denitrifiers may evolve through metabolic specialization whereas complete denitrifiers may adapt toward greater metabolic flexibility in nitrogen oxide (NOx–) utilization. Both exist within natural environments, but we lack an understanding of selective pressures driving the evolution toward each lifestyle. Here we investigate differences in growth rate, growth yield, denitrification dynamics, and the extent of intermediate metabolite accumulation under varying nutrient conditions between the model complete denitrifier Pseudomonas aeruginosa and a community of engineered specialists with deletions in the denitrification genes nar or nir. Our results in a mixed carbon medium indicate a growth rate vs. yield tradeoff between complete and partial denitrifiers, which varies with total nutrient availability and ratios of organic carbon to NOx–. We found that the cultures of both complete and partial denitrifiers accumulated nitrite and that the metabolic lifestyle coupled with nutrient conditions are responsible for the extent of nitrite accumulation.Funding for this work was provided by Simons Foundation award 622065 and an MIT Environmental Solutions Initiative seed grant to AB. Additional support was received by the MIT Ferry Fund
- …