Catalytic potential of a fungal indole prenyltransferase toward β-carbolines, harmine and harman, and their prenylation effects on antibacterial activity.

The prenylation of compounds has attracted much attention, since it often adds bioactivity to non-prenylated compounds. We employed an enzyme assay with CdpNPT, an indole prenyltransferase from Aspergillus fumigatus with two naturally occurring β-carbolines, harmine (3) and harman (4) as prenyl acceptors, in the presence of dimethylallyl diphosphate (DMAPP) as the prenyl donor. The enzyme accepted these two prenyl acceptor substrates to produce 6-(3′,3′-dimethylallyl)harmine (5) from 3 and 9-(3′,3′-dimethylallyl)harman (6) and 6-(3′,3′-dimethylallyl)harman (7) from 4. The X-ray crystal structure analysis of the CdpNPT (38–440) truncated mutant complexed with 4 , and docking simulation studies of DMAPP to the crystal structure of the CdpNPT (38–440) mutant, suggested that CdpNPT could employ the two-step prenylation mechanism to produce 7 , while the enzyme produced 6 with either one- or two-step prenylation mechanisms. Furthermore, the antibacterial assays revealed that the 3′,3′-dimethylallylation of 3 and 4 , as well as harmol (1), at C-6 enhanced the activities against Staphylococcus aureus and Bacillus subtilis. [Display omitted] • Prenylation ability of CdpNPT toward two β-carbolines was investigated. • CdpNPT accepted harmine to produce 6-(3-dimethylallyl)harmine. • CdpNPT also has the ability to produce 9- and 6-(3-dimethylallyl)harmans. • 3-Dimethylallylation of harmine and harman enhanced antibacterial activities. [ABSTRACT FROM AUTHOR]