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Optimizing microbial networks through metabolic bypasses.

Enrico Orsi1, Nico J Claassens2, Pablo I Nikel3

  • 1Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.

Biotechnology Advances
|September 12, 2022
PubMed
Summary
This summary is machine-generated.

Metabolic bypasses introduce new enzyme connections, enhancing cell factory capabilities for bioproduction. This review explores how these bypasses optimize metabolism for greater efficiency and yield.

Keywords:
BottlenecksBypassCell factoriesEvolutionGrowth-coupled selectionMetabolic networksMetabolic nodes

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Area of Science:

  • Metabolic Engineering
  • Synthetic Biology
  • Biochemistry

Background:

  • Metabolism was historically viewed as rigid.
  • Recent research reveals significant metabolic plasticity in cell factories.
  • Metabolic bypasses, novel enzymatic connections, are key to this plasticity.

Purpose of the Study:

  • To review modifications in central carbon metabolism using bypasses.
  • To explore six optimization goals for bioproduction via metabolic bypasses.
  • To discuss metabolic costs and design considerations for bypass implementation.

Main Methods:

  • Introduction of heterologous enzymes to create bypasses.
  • Upregulation of native enzymes, including leveraging promiscuous activities.
  • Analysis of metabolic network modifications for bioproduction.

Main Results:

  • Bypasses expand host metabolic network capacity.
  • Optimization strategies include stoichiometric gain and overcoming kinetic/thermodynamic barriers.
  • Bypasses can circumvent toxic intermediates and uncouple production from biomass.

Conclusions:

  • Metabolic bypasses offer a powerful strategy for enhancing bioproduction.
  • Careful design is crucial to manage metabolic costs and improve yields.
  • This approach represents a significant advancement in metabolic engineering for industrial applications.