You are not currently logged in.
Access JSTOR through your library or other institution:
If You Use a Screen ReaderThis content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
PapA1 and PapA2 Are Acyltransferases Essential for the Biosynthesis of the Mycobacterium tuberculosis Virulence Factor Sulfolipid-1
Pawan Kumar, Michael W. Schelle, Madhulika Jain, Fiona L. Lin, Christopher J. Petzold, Michael D. Leavell, Julie A. Leary, Jeffery S. Cox and Carolyn R. Bertozzi
Proceedings of the National Academy of Sciences of the United States of America
Vol. 104, No. 27 (Jul. 3, 2007), pp. 11221-11226
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25436096
Page Count: 6
You can always find the topics here!Topics: Biosynthesis, Lipids, Biochemistry, Polyketides, Virulence, Enzymes, Infections, Mycobacterium tuberculosis, Bacteria, Acylation
Were these topics helpful?See somethings inaccurate? Let us know!
Select the topics that are inaccurate.
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Preview not available
Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as virulence determinants. One such glycolipid, Sulfolipid-1 (SL-1), consists of a trehalose-2-sulfate (T2S) core acylated with four lipid moieties. A diacylated intermediate in SL-1 biosynthesis, SL₁₂₇₈, has been shown to activate the adaptive immune response in human patients. Although several proteins involved in SL-1 biosynthesis have been identified, the enzymes that acylate the T2S core to form SL₁₂₇₈ and SL-1, and the biosynthetic order of these acylation reactions, are unknown. Here we demonstrate that PapA2 and PapA1 are responsible for the sequential acylation of T2S to form SL₁₂₇₈ and are essential for SL-1 biosynthesis. In vitro, recombinant PapA2 converts T2S to 2'-palmitoyl T2S, and PapA1 further elaborates this newly identified SL-1 intermediate to an analog of SL₁₂₇₈. Disruption of papA2 and papA1 in M. tuberculosis confirmed their essential role in SL-1 biosynthesis and their order of action. Finally, the △papA2 and △papA1 mutants were screened for virulence defects in a mouse model of infection. The loss of SL-1 (and SL₁₂₇₈) did not appear to affect bacterial replication or trafficking, suggesting that the functions of SL-1 are specific to human infection.
Proceedings of the National Academy of Sciences of the United States of America © 2007 National Academy of Sciences