A metabolic modeling platform for the computation of microbial ecosystems in time and space (COMETS)

Dukovski, Ilija; Bajić, Djordje; Chacón, Jeremy M.; Quintin, Michael; Vila, Jean C. C.; Sulheim, Snorre; Pacheco, Alan R.; Bernstein, David B.; Riehl, William J.; Korolev, Kirill S.; Sánchez, Álvaro; Harcombe, William R.; Segrè, Daniel

doi:10.1038/s41596-021-00593-3

Cited by 96 publications

(88 citation statements)

References 114 publications

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“…This aspect of dFBA makes it appropriate as a platform for modeling extracellular metabolic processes using standard chemical kinetics to allow molecules in the media to interact without any direct dependence on microbial biomass or metabolic models. Within the COMETS (Computation of Microbial Ecosystems in Time and Space) framework [9,46,73], dFBA has been embedded in a spatial environment, where metabolic processes are accompanied by the physical processes of molecular diffusion and biomass expansion upon growth. COMETS can therefore be used to study the spatio-temporal organization of microbial communities, with applications in multiple areas of microbial ecology [9,[47][48][49][50][51].…”

Section: Dynamic Flux Balance Analysis and Cometsmentioning

confidence: 99%

“…We have included in COMETS the capacity to handle two types of reactions which can take place in the extracellular environment. The setup for these two types of reactions is instructed in the COMETS simulation layout definition file (see [46,73]). The first type are simple massbalance equations.…”

Section: Addition Of Extracellular Reactions In Cometsmentioning

confidence: 99%

Section: Comets Simulationsmentioning

confidence: 99%

“…Simulations for all experiments were performed with COMETS version 2.9.0 [46] utilizing Gurobi version 9.0 [87]. Input file generation and output processing were performed using the COMETS Toolbox for Matlab [46]. Unless otherwise indicated, experiment parameters were set to recreate the batch culture conditions in [2].…”

Section: Comets Simulationsmentioning

confidence: 99%

“…These methods include Flux Balance Analysis (FBA) [36][37][38], initially developed for estimating the metabolic activity of individual species, and recently extended to the study of microbial communities [39-42] [5,10,43]. Dynamic Flux Balance Analysis (dFBA) [44], which iteratively updates pools of extracellular metabolites based on the fluxes observed in sequential executions of FBA, has proven particularly useful towards this goal [9,45], including through a framework called COMETS (Computation of Microbial Ecosystems in Time and Space) [9,46], which further extends dFBA to simulate the spatio-temporal organization of microbial communities [9,[47][48][49][50][51]. Despite encoding complete mechanistic models of an organism's metabolic network, FBA and dFBA approaches typically lack an explicit representation of extracellular enzyme reactions.…”

Section: Introductionmentioning

confidence: 99%

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Optimality of extracellular enzyme production and activity in dynamic flux balance modeling

Quintin

Dukovski

Bhatnagar

et al. 2021

Preprint

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In microbial communities, many vital metabolic functions, including the degradation of cellulose, proteins and other complex macromolecules, are carried out by costly, extracellularly secreted enzymes. While significant effort has been dedicated to analyzing genome-scale metabolic networks for individual microbes and communities, little is known about the interplay between global allocation of metabolic resources in the cell and extracellular enzyme secretion and activity. Here we introduce a method for modeling the secretion and catalytic functions of extracellular enzymes using dynamic flux balance analysis. This new addition, implemented within COMETS (Computation Of Microbial Ecosystems in Time and Space), simulates the costly production and secretion of enzymes and their diffusion and activity throughout the environment, independent of the producing organism. After tuning our model based on data for a Saccharomyces cerevisiae strain engineered to produce exogenous cellulases, we explored the dynamics of the system at different cellulose concentrations and enzyme production rates. We found that there are distinct rates of constitutive enzyme secretion which maximize either growth rate or biomass yield. These optimal rates are strongly dependent on enzyme kinetic properties and environmental conditions, including the amount of cellulose substrate available. Our framework will facilitate the development of more realistic simulations of microbial community dynamics within environments rich in complex macromolecules, with applications in the study of soil and plant-associated ecosystems, and other natural and engineered microbiomes.ImportanceMany organisms - including soil, marine and human-associated bacteria and fungi - perform part of their metabolic functions outside of the boundary of the cell, through the secretion of extracellular enzymes that can diffuse and facilitate reactions independently of the organism that produced them. In order to better understand and predict microbial ecosystems, it would be helpful to create mathematical models incorporating these extracellular reactions within simulations of metabolism at the whole-cell level. In this paper we demonstrate the implementation of such a methodology and apply it to study a cellulase-secreting yeast. This work will be useful for a number of microbial ecology applications, including modeling of microbiome dynamics, engineering of bioproducts (e.g. biofuels) from plant biomass through synthetic communities or modified organisms, and testing of basic ecological hypotheses about the balance between cost and benefits of the production of common goods in microbial communities.

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Section: Dynamic Flux Balance Analysis and Cometsmentioning

confidence: 99%

Section: Addition Of Extracellular Reactions In Cometsmentioning

confidence: 99%

Section: Comets Simulationsmentioning

confidence: 99%

Section: Comets Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimality of extracellular enzyme production and activity in dynamic flux balance modeling

Quintin

Dukovski

Bhatnagar

et al. 2021

Preprint

Self Cite

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Trade‐offs between the instantaneous growth rate and long‐term fitness: Consequences for microbial physiology and predictive computational models

Bruggeman¹,

Teusink²,

Steuer

2023

BioEssays

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Microbial systems biology has made enormous advances in relating microbial physiology to the underlying biochemistry and molecular biology. By meticulously studying model microorganisms, in particular Escherichia coli and Saccharomyces cerevisiae, increasingly comprehensive computational models predict metabolic fluxes, protein expression, and growth. The modeling rationale is that cells are constrained by a limited pool of resources that they allocate optimally to maximize fitness. As a consequence, the expression of particular proteins is at the expense of others, causing trade‐offs between cellular objectives such as instantaneous growth, stress tolerance, and capacity to adapt to new environments. While current computational models are remarkably predictive for E. coli and S. cerevisiae when grown in laboratory environments, this may not hold for other growth conditions and other microorganisms. In this contribution, we therefore discuss the relationship between the instantaneous growth rate, limited resources, and long‐term fitness. We discuss uses and limitations of current computational models, in particular for rapidly changing and adverse environments, and propose to classify microbial growth strategies based on Grimes's CSR framework.

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Guided by the principles of microbiome engineering: Accomplishments and perspectives for environmental use

Fang

Huang

et al. 2022

mLife

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Although the accomplishments of microbiome engineering highlight its significance for the targeted manipulation of microbial communities, knowledge and technical gaps still limit the applications of microbiome engineering in biotechnology, especially for environmental use. Addressing the environmental challenges of refractory pollutants and fluctuating environmental conditions requires an adequate understanding of the theoretical achievements and practical applications of microbiome engineering. Here, we review recent cutting-edge studies on microbiome engineering strategies and their classical applications in bioremediation. Moreover, a framework is summarized for combining both top-down and bottom-up approaches in microbiome engineering toward improved applications. A strategy to engineer microbiomes for environmental use, which avoids the build-up of toxic intermediates that pose a risk to human health, is suggested. We anticipate that the highlighted framework and strategy will be beneficial for engineering microbiomes to address difficult environmental challenges such as degrading multiple refractory pollutants and sustain the performance of engineered microbiomes in situ with indigenous microorganisms under fluctuating conditions.

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A metabolic modeling platform for the computation of microbial ecosystems in time and space (COMETS)

Cited by 96 publications

References 114 publications

Optimality of extracellular enzyme production and activity in dynamic flux balance modeling

Optimality of extracellular enzyme production and activity in dynamic flux balance modeling

Trade‐offs between the instantaneous growth rate and long‐term fitness: Consequences for microbial physiology and predictive computational models

Guided by the principles of microbiome engineering: Accomplishments and perspectives for environmental use

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