Engineering Noncanonical Cofactors To Expand Cellular Functions.
Samuel Lim1,2, Scott Banta1
1Department of Chemical Engineering, Columbia University, New York, New York 10027, United States.
ACS Synthetic Biology
|September 9, 2025
Summary
Synthetic biology can now control metabolic pathways using noncanonical cofactors (NCCs). This approach isolates engineered reactions, overcoming limitations of shared cofactors in host cells for novel functions.
Area of Science:
- Biochemistry
- Metabolic Engineering
- Synthetic Biology
Background:
- Heterologous enzymes are crucial for reprogramming cellular metabolism in synthetic biology.
- Shared cofactors between endogenous and introduced enzymes limit precise control over metabolic pathways.
- Noncanonical cofactors (NCCs) offer a novel solution for cofactor independence.
Purpose of the Study:
- To explore the potential of NCCs in synthetic biology.
- To review advancements in NCCs, their synthesis, and engineering of NCC-dependent enzymes.
- To discuss applications of NCC-utilizing cells.
Main Methods:
- Review of existing literature on NCCs and their applications.
- Analysis of cofactor sharing limitations in metabolic engineering.
- Exploration of NCC synthesis and enzyme engineering strategies.
Main Results:
- NCCs enable the isolation of specific metabolic pathways from host cell machinery.
- This isolation circumvents thermodynamic constraints imposed by shared cofactors.
- Engineered NCC-dependent enzymes and pathways show promise for independent function.
Conclusions:
- NCCs represent a significant advancement for precise metabolic pathway control in synthetic biology.
- The independent functioning of NCC-utilizing cells opens new avenues for cellular engineering.
- Further research into NCCs and their applications will drive innovation in synthetic biology.
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