Old Yellow Enzyme (OYE) (OYE)

Old Yellow Enzyme (OYE) is a historical flavoprotein, first isolated from yeast in 1932, and serves as a paradigm for flavin-dependent oxidoreductases [1, 7, 11, 22]. It contains a flavin mononucleotide (FMN) cofactor and primarily catalyzes the asymmetric reduction of alpha,beta-unsaturated carbonyl compounds (activated alkenes) [2, 7, 15, 22]. While absent in humans, OYE homologs are found in bacteria, fungi, and plants, where they play roles in oxidative stress response, xenobiotic detoxification, and the maintenance of redox homeostasis [2, 3, 6, 7]. In the parasite Trypanosoma cruzi, the OYE homolog (TcOYE) functions as a prostaglandin F2alpha synthase and is a critical target for anti-chagasic drugs like nifurtimox and benznidazole [1, 5, 8, 14]. These drugs act as prodrugs that are activated by OYE-mediated reduction to generate toxic free radicals, leading to parasite cell death [1, 5, 8]. Consequently, the downregulation or loss of OYE activity is a known mechanism of drug resistance in T. cruzi [8, 14]. Beyond its role in infectious disease, OYE is widely utilized in biotechnology as a biocatalyst for the synthesis of chiral pharmaceutical intermediates [15, 17, 18, 22].

Other names

NADPH dehydrogenaseEne-reductaseProstaglandin F2alpha synthaseFlavin-dependent oxidoreductaseNADPH:acceptor oxidoreductaseOYE1OYE2OYE3

Activation of prodrugs via enzymatic reduction to generate reactive free radicals and toxic intermediates, leading to oxidative stress and cell death in pathogens [1, 5, 8].