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Related Experiment Video

Updated: Mar 12, 2026

In Vivo Monitoring of Transcriptional Activity During Metabolic Transition Using a Bioluminescent Reporter in Yeast
06:53

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Published on: February 21, 2025

954

Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast.

Drew G Michael1,2, Ezekiel J Maier1,2, Holly Brown1,2

  • 1Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, MO 63108.

Proceedings of the National Academy of Sciences of the United States of America
|November 5, 2016
PubMed
Summary

NetSurgeon, a new algorithm, identifies genetic interventions to control cell behavior. It improved ethanol production in yeast by manipulating gene expression, enhancing xylose fermentation.

Keywords:
Saccharomyces cerevisiaeengineeringgene-regulatory networksregulatory systems biologytranscriptome

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Area of Science:

  • Systems Biology
  • Synthetic Biology
  • Metabolic Engineering

Background:

  • Controlling cellular transcriptional states is crucial for medicine and bioengineering.
  • Genome-wide gene-regulatory networks offer a framework for understanding cellular control.

Purpose of the Study:

  • To develop and validate NetSurgeon, an algorithm for identifying genetic interventions to achieve desired cellular expression states.
  • To apply NetSurgeon to enhance ethanol production in Saccharomyces cerevisiae during xylose fermentation.

Main Methods:

  • Development of NetSurgeon algorithm utilizing genome-wide gene-regulatory networks.
  • Validation of NetSurgeon on existing biological datasets.
  • Application of NetSurgeon to select transcription factor deletions for improving xylose fermentation in yeast.

Main Results:

  • NetSurgeon successfully identified interventions that shifted transcriptional states towards improved fermentation.
  • Selected interventions led to significant improvements: 2.7-fold increase in xylose import, 4-fold enhancement in central carbon metabolism integration, and 1.3-fold increase in ethanol production rate.
  • Demonstrated the algorithm's efficacy in optimizing a key industrial bioprocess.

Conclusions:

  • NetSurgeon is an effective tool for rationally manipulating cellular transcriptional states.
  • The study provides a foundation for improving bioengineering applications, particularly in enhancing biofuel production.
  • An integrated model of transcriptional regulation and metabolic flux was presented for future optimization efforts.