부산대학교 도서관

In the field of natural product research, rediscovery of already-known compounds is one of the significant issues hindering new drug development. Recently, an innovative approach called bioactivity-HiTES has been developed to overcome this limitation and several new bioactive metabolites have been successfully characterized by this method. In this study, we applied bioactivity-HiTES to Corynebacterium matruchotii, an oral bacterium isolated from human dental plaque, with 3120 clinical drugs as elicitors. As a result, we identified two cryptic metabolites, methyl indole-3-acetate (4, MIAA) and indole-3-acetic acid (5, IAA), elicited by imidafenacin (1, INN), an anticholinergic agent approved by Japanese PMDA. MIAA showed weak antibacterial activity against a pulmonary disease-causing Mycobacterium conceptionense with IC50 value of 185.7μM. Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate (2, FDP) , a USFDA-approved antineoplastic agent, to 2-fluoroadenine (6, F-Ade) which displayed mild antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 μM, respectively. Finally, acelarin (3, ACR), a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis 168 with IC50 value of 33.6 μM though the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products by microbes in addition to finding cryptic metabolites in microbes.