Trends Biotechnol. 2026 Apr 1:S0167-7799(26)00095-8. doi: 10.1016/j.tibtech.2026.03.010. Online ahead of print.

ABSTRACT

Cofactor engineering is revolutionizing green biomanufacturing by overcoming the fundamental bottleneck between the limited supply/regeneration of cellular energy cofactors [e.g., NAD(P)H, ATP] and the high demands of efficient bioproduction. This review highlights advanced strategies, such as orthogonal systems that separate product synthesis pathways from basal metabolism, external energy sources (e.g., light or electricity) for cofactor regeneration, and material-enabled immobilization for scalable processes. These approaches enable high-yield production of diverse compounds, from specialized optically pure pharmaceuticals to bulk chemicals, by addressing critical limitations in yield, purity, and industrial scalability beyond conventional fermentation. Finally, we discuss challenges in process stability and economic viability, underscoring cofactor engineering’s potential as a versatile strategy for sustainable, next-generation biomanufacturing.

PMID:41927444 | DOI:10.1016/j.tibtech.2026.03.010