Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis

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• 作者：Kimberly M. Sogi ; Cynthia M. Holsclaw ; Gabriela K. Fragiadakis ; Daniel K. Nomura ; Julie A. Leary ; Carolyn R. Bertozzi
• 刊名：ACS Infectious Diseases
• 出版年：2016
• 出版时间：November 11, 2016
• 年：2016
• 卷：2
• 期：11
• 页码：800-806
• 全文大小：341K
• ISSN：2373-8227

文摘

Sulfomenaquinone (SMK) is a recently identified metabolite that is unique to the <i>Mycobacterium tuberculosisi> (<i>M. tuberculosisi>) 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 <i>stf3i>, includes a putative cytochrome P450 gene (<i>cyp128i>) and a gene of unknown function, <i>rv2269ci>. We demonstrate that <i>cyp128i> and <i>stf3i> are sufficient for the biosynthesis of SMK from menaquinone and <i>rv2269ci> exhibits promoter activity in <i>M. tuberculosisi>. 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 <i>M. tuberculosisi>. Finally, we showed in a mouse model of infection that the loss of <i>cyp128i> exhibits a hypervirulent phenotype similar to that in previous studies of the <i>stf3i> mutant. These findings provide a platform for defining the molecular basis of SMK’s role in <i>M. tuberculosisi> pathogenesis.