Engineering Microbial Metabolite Dynamics and Heterogeneity

Biotechnol J. 2017 Oct;12(10). doi: 10.1002/biot.201700422. Epub 2017 Sep 25.

Abstract

As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains.

Keywords: cell-to-cell variation; metabolic engineering; metabolite dynamics; metabolite heterogeneity; synthetic biology.

Publication types

  • Review

MeSH terms

  • Biological Products
  • Biotechnology
  • Fermentation
  • Gene Expression
  • Genetic Heterogeneity*
  • Industrial Microbiology*
  • Metabolic Engineering*
  • Metabolic Networks and Pathways
  • Synthetic Biology

Substances

  • Biological Products