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

Wu SG, He L, Wang Q, Tang YJ - Microb. Cell Fact. (2015)

Bottom Line: Current biotechnology can effectively edit the microbial genome or introduce novel enzymes to redirect carbon fluxes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Energy, Environmental and Chemical Engineering, Washington University, St. Louis, MO, 63130, USA. wug@seas.wustl.edu.

ABSTRACT
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 and energy metabolisms. The fluxomics results are essential to evaluate the industrial potential of laboratory strains, avoiding false starts and dead ends during metabolic engineering.

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Related in: MedlinePlus

Cell carbon and energy metabolism illustrated by Yin-Yang Theory (note: engineered components include plasmids, over-expressed enzymes, synthetic circuits, etc.).
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Fig1: Cell carbon and energy metabolism illustrated by Yin-Yang Theory (note: engineered components include plasmids, over-expressed enzymes, synthetic circuits, etc.).

Mentions: Heterotrophic organisms obtain free energy in the form of ATP by breaking organic substrates into CO2 (Figure 1). Theoretically, oxidation of one mole of glucose to CO2 (∆cHΘ298 ≈ −2.8 MJ/mol) can generate 38 moles of ATP. Hydrolysis of these ATP to ADP (ΔGΘ = −30.5 kJ/mol) provide ~1.2 MJ of biochemical energy. Thereby, ~60% of energy from glucose is lost as heat during ATP synthesis (similar to a Carnot heat engine). Besides, cell consumes ATP for diverse maintenance activities, such as nutrient/metabolite transport, chemotaxis, chemical gradient preservation, biomass component repair, and macromolecule re-synthesis [11]. These maintenance costs, essential for cell survival and stress adaptation, compete for ATP resources for biomass growth and product synthesis.Figure 1


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

Wu SG, He L, Wang Q, Tang YJ - Microb. Cell Fact. (2015)

Cell carbon and energy metabolism illustrated by Yin-Yang Theory (note: engineered components include plasmids, over-expressed enzymes, synthetic circuits, etc.).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374363&req=5

Fig1: Cell carbon and energy metabolism illustrated by Yin-Yang Theory (note: engineered components include plasmids, over-expressed enzymes, synthetic circuits, etc.).
Mentions: Heterotrophic organisms obtain free energy in the form of ATP by breaking organic substrates into CO2 (Figure 1). Theoretically, oxidation of one mole of glucose to CO2 (∆cHΘ298 ≈ −2.8 MJ/mol) can generate 38 moles of ATP. Hydrolysis of these ATP to ADP (ΔGΘ = −30.5 kJ/mol) provide ~1.2 MJ of biochemical energy. Thereby, ~60% of energy from glucose is lost as heat during ATP synthesis (similar to a Carnot heat engine). Besides, cell consumes ATP for diverse maintenance activities, such as nutrient/metabolite transport, chemotaxis, chemical gradient preservation, biomass component repair, and macromolecule re-synthesis [11]. These maintenance costs, essential for cell survival and stress adaptation, compete for ATP resources for biomass growth and product synthesis.Figure 1

Bottom Line: Current biotechnology can effectively edit the microbial genome or introduce novel enzymes to redirect carbon fluxes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Energy, Environmental and Chemical Engineering, Washington University, St. Louis, MO, 63130, USA. wug@seas.wustl.edu.

ABSTRACT
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 and energy metabolisms. The fluxomics results are essential to evaluate the industrial potential of laboratory strains, avoiding false starts and dead ends during metabolic engineering.

Show MeSH
Related in: MedlinePlus