Catalytic potential of a fungal indole prenyltransferase toward ß-carbolines, harmine and harman, and their prenylation effects on antibacterial activity.
J Biosci Bioeng
; 134(4): 311-317, 2022 Oct.
Article
em En
| MEDLINE
| ID: mdl-35931602
ABSTRACT
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 ß-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.
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01-internacional
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MEDLINE
Assunto principal:
Dimetilaliltranstransferase
Idioma:
En
Revista:
J Biosci Bioeng
Ano de publicação:
2022
Tipo de documento:
Article