Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase

CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a beta-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the regular-type dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His(6)-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.

Automated summary

CdpNPT, a fungal enzyme, exhibits substrate promiscuity and can generate prenylated compounds. This study reveals the catalytic potential of CdpNPT towards a beta-carboline harmol, resulting in the production of 6-(3-dimethylallyl)harmol through prenylation reaction.