Use of P450 cytochrome inhibitors in studies of enokipodin biosynthesis

Abstract

Enokipodins A, B, C, and D are antimicrobial sesquiterpenes isolated from the mycelial culture medium of Flammulina velutipes, an edible mushroom. The presence of a quaternary carbon stereocenter on the cyclopentane ring makes enokipodins A-D attractive synthetic targets. In this study, nine different cytochrome P450 inhibitors were used to trap the biosynthetic intermediates of highly oxygenated cuparene-type sesquiterpenes of F. velutipes. Of these, 1-aminobenzotriazole produced three less-highly oxygenated biosynthetic intermediates of enokipodins A-D; these were identified as (S)-(−)-cuparene-1,4-quinone and epimers at C-3 of 6-hydroxy-6-methyl-3-(1,2,2-trimethylcyclopentyl)-2-cyclohexen-1-one. One of the epimers was found to be a new compound.

1-Aminobenzotriazole: A Mechanism-Based Cytochrome P450 Inhibitor and Probe of Cytochrome P450 Biology

“…The antimicrobial sesquiterpenes enokipodins A, B, C, and D are obtained from mycelial cultures of the edible mushroom Flammulina velutipes . Studies of the biosynthesis of these agents using 1-ABT as a probe led to identification of three intermediates (shown in the boxes) in the biosynthetic sequence ( Figure 20 ) [ 321 ].…”