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Open AccessCommunication
Mar. Drugs 2011, 9(6), 984-993; doi:10.3390/md9060984

DedA Protein Relates to Action-Mechanism of Halicyclamine A, a Marine Spongean Macrocyclic Alkaloid, as an Anti-dormant Mycobacterial Substance

1
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan
2
Department of Chemistry, Faculty of Science, Lampung University, Jl. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar Lampung 35145, Indonesia
*
Authors to whom correspondence should be addressed.
Received: 1 April 2011 / Revised: 25 May 2011 / Accepted: 3 June 2011 / Published: 8 June 2011
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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.
Keywords: halicyclamine A; dedA; marine sponge; dormant; tuberculosis halicyclamine A; dedA; marine sponge; dormant; tuberculosis
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MDPI and ACS Style

Arai, M.; Liu, L.; Fujimoto, T.; Setiawan, A.; Kobayashi, M. DedA Protein Relates to Action-Mechanism of Halicyclamine A, a Marine Spongean Macrocyclic Alkaloid, as an Anti-dormant Mycobacterial Substance. Mar. Drugs 2011, 9, 984-993.

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