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A Scaffoldomics Platform for Modular In Vivo Enzyme Colocalisation and Its Application to Naringenin Biosynthesis.
Marte Elias1,2, Brecht De Paepe2, Julie Vanderstraeten1
1Laboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Ghent, Belgium.
Microbial Biotechnology
|March 12, 2026
Summary
A new scaffoldomics platform enhances microbial production of chemicals by enabling enzyme colocalisation. This synthetic biology tool significantly boosts product yield, up to 19-fold, for applications like flavonoid intermediate biosynthesis.
Area of Science:
- Synthetic biology
- Metabolic engineering
- Biocatalysis
Background:
- Microbial cell factories struggle with low product yield for fine chemical synthesis.
- Enzyme colocalisation using synthetic scaffolds can improve metabolic efficiency but current methods are inefficient.
- Developing robust platforms for enzyme complex assembly is crucial for optimizing biosynthetic pathways.
Purpose of the Study:
- To develop a versatile 'scaffoldomics' platform for combinatorial scaffolding of biosynthetic pathways.
- To enable the assembly of multi-enzyme complexes for enhanced metabolic efficiency.
- To demonstrate the platform's utility in producing naringenin, a flavonoid intermediate.
Main Methods:
- Designed a generic synthetic framework ('scaffoldomics') for assembling up to four enzymes onto a protein scaffold.
- Utilized a chromosomally encoded naringenin biosensor in Escherichia coli for real-time pathway monitoring.
- Performed comparative experiments to evaluate the impact of enzyme colocalisation on product yield.
Main Results:
- Successfully assembled multi-enzyme complexes using the scaffoldomics platform.
- Established a naringenin biosensor response curve, confirming functional production.
- Demonstrated up to a 19-fold increase in naringenin yield by incorporating enzyme colocalisation via scaffolds.
Conclusions:
- The scaffoldomics platform is a powerful tool for designing and optimizing multi-enzyme systems.
- Enzyme colocalisation significantly enhances product yield in microbial chemical production.
- This approach facilitates efficient combinatorial construction of biosynthetic pathways for synthetic biology applications.
