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Towards universal synthetic heterotrophy using a metabolic coordinator.
Sean F Sullivan1, Anuj Shetty2, Tharun Bharadwaj2
1Department of Chemical & Biological Engineering, Tufts University, Medford, MA, 02155, USA.
Metabolic Engineering
|July 5, 2023
Summary
Researchers engineered a new yeast protein, Gal3pMC, to efficiently utilize diverse non-native sugars for bioprocessing. This advance enables faster growth and better biomass production from renewable resources.
Area of Science:
- Synthetic biology and metabolic engineering
- Microbial biotechnology and bioprocessing
Background:
- Engineering Saccharomyces cerevisiae for synthetic heterotrophy allows valorization of renewable feedstocks.
- Previous work demonstrated improved growth on non-native xylose using an engineered galactose (GAL) regulon, but the system was substrate-specific.
Purpose of the Study:
- To develop a versatile GAL regulon activator for engineering synthetic heterotrophy.
- To enable the utilization of diverse non-native carbon sources in industrial yeast.
Main Methods:
- Construction and characterization of a novel Gal3p variant, Gal3pMC (metabolic coordinator).
- Molecular modeling to understand Gal3pMC conformational states.
- Testing Gal3pMC-mediated GAL regulon activation for xylose, arabinose, and cellobiose utilization in Saccharomyces cerevisiae.
Main Results:
- Gal3pMC activates the GAL regulon independently of specific inducers, mimicking native dynamics.
- Gal3pMC-based engineering resulted in higher growth rates and cell densities compared to constitutive gene overexpression.
- Demonstrated rapid and complete co-utilization of xylose, arabinose, and cellobiose.
Conclusions:
- Gal3pMC is a versatile tool for engineering synthetic heterotrophy in yeast.
- Dynamic gene expression control via GAL regulon activation by Gal3pMC offers a universally beneficial strategy for bioprocess development.
Keywords:
Gene regulationMetabolic engineeringMolecular dynamicsSubstrate utilizationSustainabilitySynthetic biologyMore Related Videos
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