Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), produces a sulfated lipid termed S881 that has been localized to the outer envelope of the cell. Mutants deficient in S881 production show a hypervirulent phenotype in the mouse model of TB infection, indicating that S881 negatively regulates the virulence of the bacterium. For six years the detailed chemical structure of this molecule was unknown due to its low abundance in crude lipid extracts.

In a recent publication, Cynthia Holsclaw in the Leary group, and her collaborators in the Bertozzi group at UC Berkeley, have characterized the structure of S881 (a novel sulfated menaquinone) through a combination of high-resolution, high-mass-accuracy, and tandem mass spectrometry. They used a Fourier-transform ion-cyclotron resonance (FT-ICR) mass spectrometer, a high-resolution instrument capable of accurate mass measurements, to determine the elemental composition of S881. In further experiments, they also used an ion trap mass spectrometer to perform tandem mass spectrometry on this molecule. Finally, synthetic structural analogs were studied to confirm the proposed structure of S881. These results demonstrate that S881 is a novel biological structure; it is a sulfated derivative of the most abundant quinol electron carrier in Mycobacterium tuberculosis. This finding represents a novel class of sulfated metabolites, and raises new questions about the functions of this redox metabolite.

The article entitled "Structural characterization of a novel sulfated menaquinone produced by stf3 from Mycobacterium tuberculosis," was published in ACS Chemical Biology in October of 2008, vol. 3 (10) pp. 619-24. Additionally, Cynthia was interviewed for the October, 2008 Podcast that complemented this article, which is available for free at
http://community.acs.org/chembiol/ under the "Podcasts" link, or through iTunes.