Ene‐Reductases‐Catalyzed Non‐Natural Reactions

Flavin‐dependent ene‐reductases (EREDs), members of the Old Yellow Enzyme (OYE) superfamily, are highly efficient biocatalysts primarily known for catalyzing the asymmetric reduction of activated alkenes. Beyond this native function, the chemical versatility of the flavin cofactor and the sophisticated architecture of their protein structures enable EREDs to exhibit catalytic multifunctionality. The catalytic promiscuity not only highlights the adaptability of these enzymes but also expands their potential to broaden the scope of enzyme‐catalyzed reactions in organic synthesis. Given the inherent challenges associated with discovering novel enzyme activities, such catalytic promiscuity of EREDs offers a promising pathway for expanding their applications. This mini‐review provides a comprehensive overview of the catalytic multifunctionality of flavin‐dependent EREDs, with a particular focus on their “non‐natural” functionalities in organic synthesis. This review is primarily divided into two main sections: hydride‐dependent reactions and hydride‐independent reactions. By highlighting these unconventional biocatalytic pathways, we aim to inspire further exploration into the untapped potential of EREDs and their role in advancing synthetic chemistry.