Genome-scale modelling of microbial metabolism with temporal and spatial resolution

Henson, Michael A.

doi:10.1042/bst20150146

Cited by 26 publications

(27 citation statements)

References 90 publications

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“…To this end, we assemble and numerically evaluate an autocatalytic genome-scale model of cyanobacterial growth, based on a highquality metabolic reconstruction of the cyanobacterium Synechococcus elongatus PCC 7942. Our model significantly improves upon previous computational analyses of diurnal phototrophic growth (14,(16)(17)(18) and takes recent developments in constraintbased analysis into account (19)(20)(21)(22). Our approach is closely related to resource balance analysis (23,24) and dynamic enzymecost flux balance analysis (25), as well as integrated metabolism and gene expression (ME) models (21,26), but explicitly accounts for the properties of diurnal phototrophic growth.…”

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confidence: 76%

“…Phototrophic growth under diurnal conditions requires a precise coordination of metabolic processes, and the resulting constraints and trade-offs are challenging to describe using constraint-based analysis and conventional FBA (20). Here, we have developed a genome-scale model that allowed us to investigate the stoichiometric and energetic constraints of diurnal phototrophic growth in the context of a global resource allocation A B Although the minimal amount of glycogen required at dusk exhibits a lower bound, cells can accumulate more glycogen with no discernible effects on overall growth yield.…”

Section: Discussionmentioning

confidence: 99%

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Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth

Reimers

Knoop

Bockmayr

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

108

130

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Cyanobacteria are an integral part of Earth's biogeochemical cycles and a promising resource for the synthesis of renewable bioproducts from atmospheric CO 2 . Growth and metabolism of cyanobacteria are inherently tied to the diurnal rhythm of light availability. As yet, however, insight into the stoichiometric and energetic constraints of cyanobacterial diurnal growth is limited. Here, we develop a computational framework to investigate the optimal allocation of cellular resources during diurnal phototrophic growth using a genome-scale metabolic reconstruction of the cyanobacterium Synechococcus elongatus PCC 7942. We formulate phototrophic growth as an autocatalytic process and solve the resulting time-dependent resource allocation problem using constraint-based analysis. Based on a narrow and well-defined set of parameters, our approach results in an ab initio prediction of growth properties over a full diurnal cycle. The computational model allows us to study the optimality of metabolite partitioning during diurnal growth. The cyclic pattern of glycogen accumulation, an emergent property of the model, has timing characteristics that are in qualitative agreement with experimental findings. The approach presented here provides insight into the time-dependent resource allocation problem of phototrophic diurnal growth and may serve as a general framework to assess the optimality of metabolic strategies that evolved in phototrophic organisms under diurnal conditions. constraint-based analysis | whole-cell models | bioenergetics | metabolism | circadian clock C yanobacterial photoautotrophic growth requires a highly coordinated distribution of cellular resources to different intracellular processes, including the de novo synthesis of proteins, ribosomes, lipids, and other cellular components. For unicellular organisms, the optimal allocation of limiting resources is a key determinant of evolutionary fitness. Owing to the importance of cellular resource allocation for understanding evolutionary trade-offs in bacterial metabolism, the cellular "protein economy" and its implications for bacterial growth laws have been studied extensively, albeit almost exclusively for heterotrophic organisms under stationary environmental conditions (1-7). For photoautotrophic organisms, including cyanobacteria, growthdependent resource allocation is further subject to diurnal lightdark (LD) cycles that partition cellular metabolism into distinct phases. Recent experimental results have demonstrated the relevance of time-specific synthesis for cellular survival and growth (8-10). Nonetheless, the implications and consequences of a diurnal environment for the cellular resource allocation problem are insufficiently understood, and computational approaches hitherto developed for heterotrophic growth are not straightforwardly applicable to diurnal phototrophic growth (11).Here, we propose a computational framework to quantitatively assess the optimality of diurnal resource allocation for phototrophic growth. We are primarily interested i...

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mentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth

Reimers

Knoop

Bockmayr

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

108

130

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“…180 Rudimentary attempts have been made to accommodate different compartments through different variables, an 'ecosystem of organelles,' or variables on different types of grids. [181][182][183][184][185][186][187] However, generally effective models and solutions are yet to be developed.…”

Section: Selecting Metabolic Rate Functions From a Smorgasbord Of Optmentioning

confidence: 99%

The best models of metabolism

Voit

2017

WIREs Mechanisms of Disease

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Biochemical systems are among of the oldest application areas of mathematical modeling. Spanning a time period of over one hundred years, the repertoire of options for structuring a model and for formulating reactions has been constantly growing, and yet, it is still unclear whether or to what degree some models are better than others and how the modeler is to choose among them. In fact, the variety of options has become overwhelming and difficult to maneuver for novices and experts alike. This review outlines the metabolic model design process and discusses the numerous choices for modeling frameworks and mathematical representations. It tries to be inclusive, even though it cannot be complete, and introduces the various modeling options in a manner that is as unbiased as that is feasible. However, the review does end with personal recommendations for the choices of default models.

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“…Similar to conventional FBA, models of this kind are not based on mechanistic insight, but rather seek to evaluate the optimality of resource allocation during phototrophic growth. It is expected that methods and applications that go beyond conventional FBA and involve spatial and temporal metabolic modeling based on genome-scale reconstructions of microbial metabolism will play an increasingly important role (Henson, 2015). …”

Section: Large-scale Models Of Cyanobacterial Metabolismmentioning

confidence: 99%

Toward Multiscale Models of Cyanobacterial Growth: A Modular Approach

Westermark

Steuer

2016

Front. Bioeng. Biotechnol.

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Oxygenic photosynthesis dominates global primary productivity ever since its evolution more than three billion years ago. While many aspects of phototrophic growth are well understood, it remains a considerable challenge to elucidate the manifold dependencies and interconnections between the diverse cellular processes that together facilitate the synthesis of new cells. Phototrophic growth involves the coordinated action of several layers of cellular functioning, ranging from the photosynthetic light reactions and the electron transport chain, to carbon-concentrating mechanisms and the assimilation of inorganic carbon. It requires the synthesis of new building blocks by cellular metabolism, protection against excessive light, as well as diurnal regulation by a circadian clock and the orchestration of gene expression and cell division. Computational modeling allows us to quantitatively describe these cellular functions and processes relevant for phototrophic growth. As yet, however, computational models are mostly confined to the inner workings of individual cellular processes, rather than describing the manifold interactions between them in the context of a living cell. Using cyanobacteria as model organisms, this contribution seeks to summarize existing computational models that are relevant to describe phototrophic growth and seeks to outline their interactions and dependencies. Our ultimate aim is to understand cellular functioning and growth as the outcome of a coordinated operation of diverse yet interconnected cellular processes.

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Genome-scale modelling of microbial metabolism with temporal and spatial resolution

Cited by 26 publications

References 90 publications

Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth

Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth

The best models of metabolism

Toward Multiscale Models of Cyanobacterial Growth: A Modular Approach

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