Arai, Masayoshi and Yamano, Yoshi and Setiawan, Andi and Kobayashi, Motomasa Identification of the Target Protein of Agelasine D, a Marine Sponge Diterpene Alkaloid, as an Anti-dormant Mycobacterial Substance. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Abstract

One of the major reasons for the wide epidemicity of tubercu�losis and for the necessity for extensive chemotherapeutic regi�mens is that the causative agent, Mycobacterium tuberculosis, has an ability to become dormant. Therefore, new lead com�pounds that are anti-bacterial against M. tuberculosis in both active and dormant states are urgently needed. Marine sponge diterpene alkaloids, agelasines B, C, and D, from an Indonesian marine sponge of the genus Agelas were rediscovered as anti�dormant-mycobacterial substances. Based on the concept that the transformants over-expressing targets of antimicrobial sub�stances confer drug resistance, strains resistant to agelasine D were screened from Mycobacterium smegmatis transformed with a genomic DNA library of Mycobacterium bovis BCG. Se�quence analysis of the cosmids isolated from resistant trans�formants revealed that the responsible gene was located in the genome region between 3475.051 and 3502.901 kb. Fur�ther analysis of the transformants over-expressing the individu�al gene contained in this region indicated that BCG3185c (pos�sibly a dioxygenase) might be a target of the molecule. More�over, agelasine D was found to bind directly to recombinant BCG3185c protein (KD 2.42 mm), based on surface plasmon res�onance (SPR). This evidence strongly suggests that the BCG3185c protein is the major target of agelasine D, and that the latter is the anti-mycobacterial substance against dormant bacilli.

Item Type: Other
Subjects: Q Science > Q Science (General)
Depositing User: Dr. Andi Setiawan
Date Deposited: 15 Feb 2022 01:11
Last Modified: 15 Feb 2022 01:11
URI: http://repository.lppm.unila.ac.id/id/eprint/39227

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