Search for mechanism of action of novel pyrano[3,2-b]indolones: genome sequencing of Mycobacterium bovis BCG parent strain and resistant mutant

Isolation of Mycobacterium bovis BCG mutat resistant to the lead compound 10a allowed comparative analysis of its genome with the parent strain. It revealed that the mutant strain harbors deletion of a significant portion of the fgd1 gene, encoding F-420-dependent glucose-6-phosphate dehydrogenase, explaining observed phenotypic changes in the mutant. This information along with our additional data led us to conclude that 10a is a pro-drug that is activated by an unknown F-420-dependent enzyme of tuberculosis bacteria.