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Protocol for condition-dependent metabolite yield prediction using the TRIMER pipeline.

Puhua Niu1, Maria J Soto2, Byung-Jun Yoon1,3

  • 1Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.

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|March 4, 2022
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Summary
This summary is machine-generated.

This study introduces TRIMER, a computational tool for predicting metabolite yields. TRIMER integrates gene regulatory and metabolic networks to guide metabolic engineering strategies in microbes like E. coli and yeast.

Keywords:
BioinformaticsCell BiologyGene ExpressionMetabolismSystems biology

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Area of Science:

  • Computational Biology
  • Metabolic Engineering
  • Systems Biology

Background:

  • Metabolic engineering relies on understanding gene regulation and metabolic flux.
  • Predicting the impact of genetic modifications, especially transcription factor (TF) deletions, is crucial for optimizing metabolite production.
  • Existing models often struggle to integrate transcriptional regulation with metabolic networks effectively.

Purpose of the Study:

  • To present a novel computational pipeline, TRIMER (Transcription Regulation Integrated with MEtabolic Regulation), for condition-dependent metabolite yield prediction.
  • To develop a hybrid model that integrates transcription factor (TF)-gene regulatory networks (TRNs) with Bayesian networks (BNs) for enhanced metabolic reaction regulation.
  • To provide a scalable method for predicting knockout phenotypes and metabolic fluxes in microbial systems.

Main Methods:

  • Developed TRIMER, a hybrid computational model combining TRNs and BNs.
  • Inferred BNs from transcriptomic expression data to model metabolic reactions.
  • Integrated TF-gene regulatory information with metabolic network models.
  • Applied the pipeline to genome-scale models of *E. coli* and yeast.

Main Results:

  • TRIMER accurately predicts condition-dependent metabolite yields.
  • The model successfully forecasts knockout phenotypes and metabolic fluxes resulting from TF deletions.
  • Demonstrated reliable predictions for both *E. coli* and yeast at the genome scale.
  • The hybrid approach effectively regulates metabolic reactions by integrating transcriptional and metabolic information.

Conclusions:

  • TRIMER offers a robust framework for metabolite yield prediction in metabolic engineering.
  • The integration of transcriptional regulation with metabolic networks is key to improving predictive accuracy.
  • This protocol facilitates the design of more effective genetic modifications for microbial cell factories.