Journal
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
Volume 134, Issue 4, Pages 311-317Publisher
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2022.07.004
Keywords
Prenylation; fl-Carboline; Harmine; Harman; Indole prenyltransferase]
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan (JSPS KAKENHI) [22H02777, 22K15303]
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This study investigated the prenylation of naturally occurring β-carbolines and elucidated the prenylation mechanism using enzyme assay, X-ray crystal structure analysis, and docking simulation studies. Moreover, antibacterial assays revealed that specific prenylation enhanced the antimicrobial activities of the compounds.
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 b-carbolines, harmine (3) and harman (4) as prenyl acceptors, in the presence of dime-thylallyl 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)har-man (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.(c) 2022, The Society for Biotechnology, Japan. All rights reserved.
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