The regulatory mechanism of carbon metabolism in the microbial center under changing environment

Metabolism is the basis for all life activities of organisms.
Analyzing the complex mechanism behind metabolic regulation is the key to a deep understanding of organisms.
However, revealing the response and regulation mechanisms of organisms in different environments has always been a difficult problem in biology
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Recently, the research group of Prof.
Markus Basan from the Department of Systems Biology at Harvard University and the research group of Prof.
Uwe Sauer from the Department of Molecular Systems Biology at ETH Zurich (jointly as Severin Josef Schink and Dimitris Christodoulou) published the cover article Glycolysis in Molecular Systems Biology.
/gluconeogenesis specialization in microbes is driven by biochemical constraints of flux sensing
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This study starts with the basic metabolic regulation of microorganisms, and uses multi-omics data and mechanism modeling to reveal the regulatory mechanisms of microorganisms on two opposite central carbon metabolism pathways, glycolysis and gluconeogenesis, in a changing environment.

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Due to the cross-species conservation (similarity) of metabolism, this novel research method through mechanistic modeling can also be applied to the study of human cellular metabolism, further advancing the process of decoding complex diseases in humans
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Mechanism modeling subverts traditional research and development methods and can provide more accurate professional insights.
By quickly generating and verifying a large number of hypotheses before entering experiments, it can efficiently enable biological research, and on the basis of improving people's understanding of microbial metabolism, It will bring new inspiration to explore the human metabolic regulatory network and more life sciences
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Cover note for the January issue of Molecular Systems Biology In this work, Dr.
Dimitris Christodoulou and collaborators propose a coarse-grained kinetic model of central carbon metabolism that elucidates the effect of central carbon metabolism on substrate availability and general availability.
Quantity requires significant self-organization capabilities
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During exponential growth, regulatory metabolites tune the system to a steady state away from equilibrium, providing cells with an ingenious mechanism to sense the desired direction of flux
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The model also revealed a critical limitation of this flux perception
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Coarse-grained kinetic model of central carbon metabolism In nature, microorganisms are in a changing environment, and their adaptability to the environment has therefore become an important factor to measure their health.
However, scientists still lack the physiological mechanism of microbial growth and transformation Understanding, in particular, what determines the adaptive strategies of microorganisms under defined conditions
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The deprivation of microbes of major nutrients is one such environmental change.
In response to such environmental changes, how microbes self-regulate, this paper explores the role of Escherichia coli, Pseudomonas aeruginosa and Pseudomonas putida in glycolysis and gluconeogenesis.
Dynamic reorganization of central metabolism after switching between these two opposing central carbon metabolism pathway configurations
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Models for studying the reorganization process of glycolysis or gluconeogenesis have revealed a fundamental limitation of regulatory networks: Following nutrient transfer, metabolite concentrations plummet to an equilibrium point, leaving cells unable to sense the direction of flux flowing through the metabolic network
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Cells can partially alleviate this by choosing the preferred direction of regulation, but by increasing the lag time in the opposite direction of regulation
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In addition, shortening both lag times simultaneously results in a decrease in growth rate or an increase in ineffective cycling between metabolic enzymes
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The balance of these three may explain why different microbial species have preferences for substrates for glycolysis or gluconeogenesis, while helping to elucidate the complex growth patterns exhibited by different microbial species
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Studies have shown that, at least based on existing allosteric and transcriptional regulation, the above balance can be identified as an intrinsic property of central carbon metabolism
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Microbial species can only proliferate maximally within the Pareto boundaries created by these equilibria, which can lead to the evolution of substrate specificity
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The researchers found a reversal of substrate preference in P.
aeruginosa compared to E.
coli, consistent with a complete reversal of the phenomenon of lag phase and metabolite kinetics
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In Pseudomonas putida, the researchers discovered a general strategy with moderate lag times in both directions
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The regulatory structure of central metabolism enables efficient regulation of fluxes and metabolite pools in response to different external conditions, avoids toxic accumulation of internal metabolites, and integrates multiple conflicting signals through only two regulatory nodes
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Central metabolism is an excellent example of the self-organization of regulatory networks in biology
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It provides an ingenious solution to a complex and must-answer biochemical question in central carbon metabolism, explaining why we find the transition between glycolytic and gluconeogenic conditions to be so conserved across different microbial species high
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