期刊
CELL CHEMICAL BIOLOGY
卷 23, 期 6, 页码 666-677出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2016.05.011
关键词
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资金
- NIH [K08AI085033, R03MH087444]
- Bill and Melinda Gates Foundation
- Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), NIH, Department of Health and Human Services [U19AI110818]
Successful treatment of Mycobacterium tuberculosis infection typically requires a complex regimen administered over at least 6 months. Interestingly, many of the antibiotics used to treat M. tuberculosis are prodrugs that require intracellular activation. Here, we describe three small molecules, active against both replicating and non-replicating M. tuberculosis, that require activation by Baeyer-Villiger monooxygenases (BVMOs). Two molecules require BVMO EthA (Rv3854c) for activation and the third molecule requires the BVMO MymA (Rv3083). While EthA is known to activate the antitubercular drug ethionamide, this is the first description of MymA as an activating enzyme of a prodrug. Furthermore, we found that MymA also plays a role in activating ethionamide, with loss of MymA function resulting in ethionamide resistant M. tuberculosis. These findings suggest overlap in function and specificity of the BVMOs in M. tuberculosis.
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