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Title: An ancient Chinese wisdom for metabolic engineering: Yin-Yang

In ancient Chinese philosophy, Yin-Yang describes two contrary forces that are interconnected and interdependent. This concept also holds true in microbial cell factories, where Yin represents energy metabolism in the form of ATP, and Yang represents carbon metabolism. Current biotechnology can effectively edit the microbial genome or introduce novel enzymes to redirect carbon fluxes. On the other hand, microbial metabolism loses significant free energy as heat when converting sugar into ATP; while maintenance energy expenditures further aggravate ATP shortage. The limitation of cell “powerhouse” prevents hosts from achieving high carbon yields and rates. Via an Escherichia coli flux balance analysis model, we further demonstrate the penalty of ATP cost on biofuel synthesis. To ensure cell powerhouse being sufficient in microbial cell factories, we propose five principles: 1. Take advantage of native pathways for product synthesis. 2. Pursue biosynthesis relying only on pathways or genetic parts without significant ATP burden. 3. Combine microbial production with chemical conversions (semi-biosynthesis) to reduce biosynthesis steps. 4. Create “minimal cells” or use non-model microbial hosts with higher energy fitness. 5. Develop a photosynthesis chassis that can utilize light energy and cheap carbon feedstocks. Meanwhile, metabolic flux analysis can be used to quantify both carbon andmore » energy metabolisms. The fluxomics results are essential to evaluate the industrial potential of laboratory strains, avoiding false starts and dead ends during metabolic engineering« less
 [1] ;  [1] ;  [2] ;  [1]
  1. Washington Univ., St. Louis, MO (United States). Environmental and Chemical Engineering
  2. BASF Corporation, Tarrytown, NY (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
SC0012722; DBI-1356669; MCB0954016
Accepted Manuscript
Journal Name:
Microbial Cell Factories
Additional Journal Information:
Journal Volume: 14; Journal Issue: 1; Journal ID: ISSN 1475-2859
BioMed Central
Research Org:
Washington Univ., St. Louis, MO (United States)
Sponsoring Org:
USDOE Office of Science (SC); National Science Foundation
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES ATP; energy metabolism; flux analysis; free energy; maintenance loss; semi-biosynthesis