Redox Cofactor Diversity in Biological Hydride Transfer Reactions

Abstract Hydride-transfer reactions play central roles in biological redox chemistry across all domains of life. These transformations rely on specialized cofactors that enable the efficient transfer of reducing equivalents in oxidoreductive reactions. Nature has evolved several cofactors for this purpose, including nicotinamides, flavins, F420, pyrroloquinolone quinone (PQQ), and mycofactocin (MFT). Although these cofactors perform related functions, they differ in their structure, redox properties, reaction mechanisms, and biological distribution. This Review outlines these cofactors, highlighting common themes in hydride transfer mechanisms and how cofactor chemistry is linked to their biological function. In particular, F420, PQQ, and MFT are niche cofactors that expand our understanding of the diversity of cofactors and redox metabolism. Ultimately, understanding the chemistry and biology of redox cofactors offers broader applications in biotechnology and biocatalysis.