Transformation of a monoterpene ketone, (R)-(+)-pulegone, a potent hepatotoxin, in Mucor piriformis

Biotransformation of a monoterpene ketone, (R)-(+)-pulegone (I), a potent h epatotoxin, was studied using a fungal strain, Mucor piriformis. Eight meta bolites, namely, 5-hydroxypulegone (II), piperitenone (III), 6-hydroxypuleg one (TV), 3-hydroxypulegone (V), 5-methyl-2-(1-hydroxy-1-methylethyl)-2-cyc lohexene-1-one (VI), 3-hydroxyisopulegone (VII), 7-hydroxypiperitenone (VII I), and 7-hydroxypulegone (IX), have been isolated from the fermentation me dium and identified. GC analysis of the metabolites indicated that II was t he major metabolite formed. The organism initiates transformation either by hydroxylation at the C-5 position or by hydroxylation of the ring methylen es, the former being the major activity. On the basis of the identification of the metabolites, pathways for the biotransformation of (R)-(+)-pulegone have been proposed. The mode of transformation of (S)-(-)-pulegone by this organism was shown to be similar to that of its (R)-(+)-enantiomer. When i sopulegone (X) was used as the substrate, the organism isomerized it to pul egone (I), which was then transformed to metabolites II-IX.