期刊
ACS INFECTIOUS DISEASES
卷 2, 期 11, 页码 800-806出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.6b00106
关键词
Mycobacterium tuberculosis; menaquinone; cell wall; cytochrome P450; lipids; mass spectrometry
资金
- National Institutes of Health [R01 AI051622]
- Howard Hughes Medial Institute
- NCI [R01 CA172667, R01 GM47356]
Sulfomenaquinone (SMK) is a recently identified metabolite that is unique to the Mycobacterium tuberculosis (M. tuberculosis) complex and is shown to modulate its virulence. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. We demonstrate that cyp128 and stf3 are sufficient for the biosynthesis of SMK from menaquinone and rv2269c exhibits promoter activity in M. tuberculosis. Loss of Stf3 expression, but not that of Cyp128, is correlated with elevated levels of menaquinone-9, an essential component in the electron transport chain in M. tuberculosis. Finally, we showed in a mouse model of infection that the loss of cyp128 exhibits a hypervirulent phenotype similar to that in previous studies of the stf3 mutant. These findings provide a platform for defining the molecular basis of SMK's role in M. tuberculosis pathogenesis.
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