AmAT19, an acetyltransferase from Astragalus membranaceus, catalyses specific 6α-OH acetylation for tetracyclic triterpenes and steroids

Tetracyclic triterpenes and steroids are pharmacologically important molecules, and acetylation could improve their bioactivities. In this study, a highly regio- and stereo-specific acetyltransferase, AmAT19, was discovered from Astragalus membranaceus. AmAT19 could selectively catalyze the 6 alpha-OH acetylation of four tetracyclic triterpenes and steroids. The strict selectivity is associated with different orientations of the 6 alpha/beta-OH as indicated by molecular docking. Acetylated products 1a, 3a and 4a remarkably increased the inhibitory activity against the 3-chymotrypsin-like protease (3CL(pro)) of SARS-CoV-2, compared to 1, 3, and 4. AmAT19 could be a promising catalyst for specific 6 alpha-OH acetylation to expand the molecular diversity of triterpenes and steroids.

Automated summary

A highly regio- and stereo-specific acetyltransferase, AmAT19, was discovered from Astragalus membranaceus, which could selectively catalyze the 6 alpha-OH acetylation of tetracyclic triterpenes and steroids. The acetylated products showed increased inhibitory activity against SARS-CoV-2, suggesting AmAT19 as a promising catalyst for enhancing the bioactivities of these molecules and expanding their diversity.