Enzymatic deglycosylation of enfumafungin, a triterpene glycoside natural product, and its chemically synthesized analogues

A panel of 27 commercial enzymes was screened for the deglycosylation of a triterpene glycoside (enfumafungin), an antifungal natural product with a novel mechanism of action that bears an ester, a hemi-acetal and a carboxylic acid functionalities in its structures. Only one enzyme, a recombinant β-d-glucosidase, was identified which catalyzed the desired deglycosylation with the formation of the aglycone moiety that also bears an ester, a hemi-acetal and a carboxylic acid functionalities. Several chemical analogues of this natural product, whose ester moieties had been removed by chemical hydrolysis, were also screened and shown to be susceptible to deglycosylation by eight of the enzymes in the panel. These enzymes included one β-glucuronidase and six thermophilic glycosidases in addition to the recombinant β-d-glucosidase. Scaled-up synthesis of the intact aglycones, using recombinant β-d-glucosidase and β-glucuronidase, reaffirmed the catalytic utility of selected enzymes in large-scale organic synthetic reactions.