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Assessing Energy Substrate Oxidation In Vitro with 14CO2 Trapping
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Synergistic substrate cofeeding stimulates reductive metabolism
Junyoung O Park1,2, Nian Liu1, Kara M Holinski1
1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature Metabolism
|July 23, 2020
Summary
This study shows how to enhance bioproduct synthesis by "doping" microbes with specific sugars. This strategy overcomes natural metabolic limits, enabling efficient carbon dioxide conversion into valuable products.
Area of Science:
- Metabolic Engineering
- Synthetic Biology
- Biotechnology
Background:
- Efficient bioproduct synthesis relies on balancing carbon, ATP, and reducing agents.
- Native metabolic pathways often prevent co-utilization of multiple substrates due to regulatory mechanisms like catabolite repression.
Purpose of the Study:
- To explore mixed substrate metabolism for synergistic stimulation of carbon reduction.
- To develop a method for controlling pathway usage to enhance bioproduct synthesis.
Main Methods:
- Controlled co-feeding of superior ATP and NADPH generating substrates ('dopants') to microbial cultures.
- Circumventing catabolite repression by strategic substrate addition.
- Investigating synergistic effects in two divergent organisms: Moorella thermoacetica and Yarrowia lipolytica.
Main Results:
- Glucose doping in M. thermoacetica enhanced CO2 reduction to acetate (2.3 g/gCDW/h) by boosting ATP synthesis.
- Gluconate doping in Y. lipolytica accelerated acetate-driven lipogenesis (0.046 g/gCDW/h) via NADPH production.
- Synergistic cofeeding yielded CO2-derived lipids with 38% energy efficiency.
Conclusions:
- Controlled substrate co-feeding is a viable strategy to overcome metabolic limitations and enhance bioproduct synthesis.
- This approach demonstrates significant potential for converting CO2 into advanced bioproducts, addressing a key challenge in carbon utilization.
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