Journal
TRENDS IN BIOTECHNOLOGY
Volume 34, Issue 8, Pages 652-664Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tibtech.2016.02.010
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Funding
- National Science Foundation (NSF) [MCB 1448657, DBI 1356669]
- Department of Energy [DESC0012722]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1356669] Funding Source: National Science Foundation
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1448657] Funding Source: National Science Foundation
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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), C-13-metabolic flux analysis (MFA), and machine-learning approaches are needed for weighting, standardizing, and predicting metabolic costs.
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