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In Vivo Monitoring of Transcriptional Activity During Metabolic Transition Using a Bioluminescent Reporter in Yeast

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Computational study on ratio-sensing in yeast galactose utilization pathway.

Jiayin Hong¹, Bo Hua², Michael Springer²

¹Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.

Plos Computational Biology

|December 4, 2020

Summary

This summary is machine-generated.

Microbial gene expression responds to nutrient signals, with yeast galactose genes exhibiting ratio-sensing, not just glucose repression. This regulation involves competition for transporters and transcription factors, offering insights for synthetic biology.

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Area of Science:

Systems Biology
Molecular Biology
Metabolic Engineering

Background:

Microbial metabolic networks regulate gene expression based on external nutrient availability.
Catabolite repression typically shuts down alternative carbon source metabolism when glucose is present.
Recent findings suggest yeast galactose gene induction depends on the galactose-to-glucose ratio, not solely glucose absence.

Purpose of the Study:

To elucidate the mechanism behind ratio-sensing in the yeast galactose metabolic network.
To investigate how competition at transporter and regulatory levels contributes to ratio-sensing.
To explore how circuit topology influences the sensitivity and dynamics of nutrient signal processing.

Main Methods:

Mathematical modeling was employed to simulate and analyze ratio-sensing phenomena.
Analysis focused on competitive interactions between carbon sources for shared transporters and transcription factors.
The impact of circuit topology, including negative auto-regulation and feedforward loops, was investigated.

Main Results:

Ratio-sensing can emerge from competition for shared transporters, transcription factors, or both.
Combining both competition layers expands the dynamic range of ratio-sensing.
Negative auto-regulation and coherent feedforward loops enhance sensitivity to nutrient signals.

Conclusions:

The study reveals the underlying mechanisms of ratio-sensing in yeast GAL metabolic regulation.
Identified design principles for ratio-sensing signal processing applicable to other biological systems.
Findings provide a foundation for engineering ratio-sensing circuits in synthetic biology.