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Related Concept Videos

Fermentation01:24

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FermentationFermentation is a metabolic process that allows organisms to produce energy in the absence of oxygen. It occurs in microorganisms and specific animal cells and partially breaks down glucose. Unlike aerobic respiration, fermentation produces less ATP but enables survival in low-oxygen environments. There are different types of fermentation, such as lactic acid fermentation (which occurs in muscle cells) and alcoholic fermentation (used by yeast and bacteria).Science and Engineering...
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Using Kinetic Modelling to Infer Adaptations in Saccharomyces cerevisiae Carbohydrate Storage Metabolism to Dynamic

David Lao-Martil1, Koen J A Verhagen2, Ana H Valdeira Caetano2

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This study investigates how Saccharomyces cerevisiae adapts to changing conditions in industrial bioreactors. It reveals key metabolic adjustments and identifies areas needing further research for better process control.

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Area of Science:

  • Biotechnology and metabolic engineering
  • Microbial physiology and systems biology
  • Biochemical engineering

Background:

  • Industrial bioreactors present dynamic and inhomogeneous conditions, unlike controlled lab environments.
  • Understanding Saccharomyces cerevisiae's response to these perturbations is crucial for optimizing bioprocesses.
  • Current mechanistic understanding of yeast adaptation to frequent substrate changes is limited.

Purpose of the Study:

  • To mechanistically understand Saccharomyces cerevisiae's metabolic adjustments to prolonged dynamic conditions in bioreactors.
  • To integrate multi-omics data with kinetic metabolic modeling for predicting cellular responses.
  • To identify key enzymes and regulatory mechanisms involved in adaptation to substrate perturbations.

Main Methods:

  • Combined quantitative metabolomics, 13C enrichment, and flux quantification data.
  • Applied kinetic metabolic modeling to analyze intracellular metabolic response dynamics.
  • Developed a novel parameter estimation pipeline using combinatorial enzyme selection and regularization.

Main Results:

  • Predicted and confirmed proteomic changes in hexose transport and phosphorylation reactions.
  • Identified minimum enzyme and parameter adjustments required for steady-state to dynamic transitions.
  • Revealed discrepancies between mechanistic rate laws and observed intracellular fluxes, including hexose transport and trehalase activity.

Conclusions:

  • The study provides insights into Saccharomyces cerevisiae's adaptation strategies under dynamic industrial bioreactor conditions.
  • The developed modeling approach successfully predicted some proteomic changes.
  • Unexplained kinetic or regulatory phenomena warrant further investigation for a complete mechanistic understanding.