Metabolic Burden: Cornerstones in Synthetic Biology and Metabolic Engineering Applications

Trends Biotechnol. 2016 Aug;34(8):652-664. doi: 10.1016/j.tibtech.2016.02.010. Epub 2016 Mar 18.


Engineering cell metabolism for bioproduction not only consumes building blocks and energy molecules (e.g., ATP) but also triggers energetic inefficiency inside the cell. The metabolic burdens on microbial workhorses lead to undesirable physiological changes, placing hidden constraints on host productivity. We discuss cell physiological responses to metabolic burdens, as well as strategies to identify and resolve the carbon and energy burden problems, including metabolic balancing, enhancing respiration, dynamic regulatory systems, chromosomal engineering, decoupling cell growth with production phases, and co-utilization of nutrient resources. To design robust strains with high chances of success in industrial settings, novel genome-scale models (GSMs), (13)C-metabolic flux analysis (MFA), and machine-learning approaches are needed for weighting, standardizing, and predicting metabolic costs.

Keywords: (13)C-MFA; chromosomal engineering; genome-scale model; machine learning.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Physiological Phenomena*
  • Bioreactors / microbiology
  • Carbon / metabolism*
  • Energy Metabolism / physiology
  • Genetic Enhancement / methods
  • Metabolic Engineering / methods*
  • Metabolic Flux Analysis / methods*
  • Metabolic Networks and Pathways / physiology*
  • Metabolome / physiology*
  • Models, Biological
  • Synthetic Biology / methods*


  • Carbon