title: DedA protein relates to action-mechanism of halicyclamine A, a marine spongean macrocyclic alkaloid, as an anti-dormant mycobacterial substance.
abstract: A macrocyclic alkaloid, halicyclamine A, was re-discovered from an Indonesian marine sponge of Haliclona sp. 05A08 as an anti-dormant mycobacterial substance. To clarify action-mechanism of halicyclamine A, halicyclamine A-resistant strains were screened from the transformants of Mycobacterium smegmatis with the genomic DNA library of M. bovis BCG, which were constructed in the multi-copy shuttle cosmid pYUB145. Sequencing analysis of the cosmids isolated from the halicyclamine A-resistant transformants revealed that the responsible gene was involved in the genome region between 2920.549 kb and 2933.210 kb. Further experiments using the transformants over-expressing individual gene contained in the responsible region were executed, and the transformant, which over-expressed BCG2664 gene assigned as dedA gene, was found to become halicyclamine A-resistant. This evidence strongly suggested that DedA protein correlates with the action-mechanism of halicyclamine A as an anti-dormant mycobacterial substance.
authors: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors: Masayoshi
authors: M
authors: Arai
authors: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors: Liu
authors: L
authors: Liu
authors: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors: Takao
authors: T
authors: Fujimoto
authors: Department of Chemistry, Faculty of Science, Lampung University, Jl. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar Lampung 35145, Indonesia.
authors: Andi
authors: A
authors: Setiawan
authors: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors: Motomasa
authors: M
authors: Kobayashi
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D003360:Cosmids / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015698:Genomic Library; D007214:Indonesia; D047028:Macrocyclic Compounds / Q000494:pharmacology*; D009161:Mycobacterium / Q000187:drug effects* / Q000235:genetics; D009163:Mycobacterium bovis / Q000235:genetics; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics; D010880:Piperidines / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry
chemical_list: D000470:Alkaloids; D001426:Bacterial Proteins; D001643:Bridged Bicyclo Compounds; D047028:Macrocyclic Compounds; D010880:Piperidines; C482962:halicyclamine A