A versatile in situ cofactor enhancing system for meeting cellular demands for engineered metabolic pathways
Issued Date
2024-02-01
Resource Type
ISSN
00219258
eISSN
1083351X
Scopus ID
2-s2.0-85184079821
Pubmed ID
38159859
Journal Title
Journal of Biological Chemistry
Volume
300
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Biological Chemistry Vol.300 No.2 (2024)
Suggested Citation
Jaroensuk J., Sutthaphirom C., Phonbuppha J., Chinantuya W., Kesornpun C., Akeratchatapan N., Kittipanukul N., Phatinuwat K., Atichartpongkul S., Fuangthong M., Pongtharangkul T., Hollmann F., Chaiyen P. A versatile in situ cofactor enhancing system for meeting cellular demands for engineered metabolic pathways. Journal of Biological Chemistry Vol.300 No.2 (2024). doi:10.1016/j.jbc.2023.105598 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97158
Title
A versatile in situ cofactor enhancing system for meeting cellular demands for engineered metabolic pathways
Corresponding Author(s)
Other Contributor(s)
Abstract
Cofactor imbalance obstructs the productivities of metabolically engineered cells. Herein, we employed a minimally perturbing system, xylose reductase and lactose (XR/lactose), to increase the levels of a pool of sugar phosphates which are connected to the biosynthesis of NAD(P)H, FAD, FMN, and ATP in Escherichia coli. The XR/lactose system could increase the amounts of the precursors of these cofactors and was tested with three different metabolically engineered cell systems (fatty alcohol biosynthesis, bioluminescence light generation, and alkane biosynthesis) with different cofactor demands. Productivities of these cells were increased 2-4-fold by the XR/lactose system. Untargeted metabolomic analysis revealed different metabolite patterns among these cells, demonstrating that only metabolites involved in relevant cofactor biosynthesis were altered. The results were also confirmed by transcriptomic analysis. Another sugar reducing system (glucose dehydrogenase) could also be used to increase fatty alcohol production but resulted in less yield enhancement than XR. This work demonstrates that the approach of increasing cellular sugar phosphates can be a generic tool to increase in vivo cofactor generation upon cellular demand for synthetic biology.