ArticleThe Journal of biological chemistry2012
Elucidation and chemical modulation of sulfolipid-1 biosynthesis in Mycobacterium tuberculosis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
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- Structure, assembly, and mechanism of the MmpL family of transporters.Microbiology and molecular biology reviews : MMBR · 2026Review
- Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.Science advances · 2025Article
- Deciphering tuberculosis: lysosome-centric insights into pathogenesis and therapies.Frontiers in cellular and infection microbiology · 2025Review
- Approaches to stereoselective 1,1'-glycosylation.Beilstein journal of organic chemistry · 2025Review
- Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.PLoS biology · 2024Article
- Betaine and I-LG may have a predictive value for ATB: A causal study in a large European population.PloS one · 2024Article
- A Loss of Function in LprG-Rv1410c Homologues Attenuates Growth during Biofilm Formation inPathogens (Basel, Switzerland) · 2023Article
- Structural basis for the development of potential inhibitors targeting FadD23 from Mycobacterium tuberculosis.Acta crystallographica. Section F, Structural biology communications · 2023Article
- Construction of a Bacterial Lipidomics Analytical Platform: Pilot Validation with Bovine Paratuberculosis Serum.Metabolites · 2023Article
- Target Identification in Anti-Tuberculosis Drug Discovery.International journal of molecular sciences · 2023Review
- The Key Roles ofFrontiers in microbiology · 2023Article
- Versatile approach towards fully desymmetrized trehalose with a novel set of orthogonal protecting groups.Frontiers in chemistry · 2023Article
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- Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell Envelope.Chemical reviews · 2021Review
- Glycoconjugate pathway connections revealed by sequence similarity network analysis of the monotopic phosphoglycosyl transferases.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Various Facets of Pathogenic Lipids in Infectious Diseases: Exploring Virulent Lipid-Host Interactome and Their Druggability.The Journal of membrane biology · 2020Review
- The final assembly of trehalose polyphleates takes place within the outer layer of the mycobacterial cell envelope.The Journal of biological chemistry · 2020Article
- Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis.mSystems · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis possesses unique cell-surface lipids that have been implicated in virulence. One of the most abundant is sulfolipid-1 (SL-1), a tetraacyl-sulfotrehalose glycolipid. Although the early steps in SL-1 biosynthesis are known, the machinery underlying the final acylation reactions is not understood. We provide genetic and biochemical evidence for the activities of two proteins, Chp1 and Sap (corresponding to gene loci rv3822 and rv3821), that complete this pathway. The membrane-associated acyltransferase Chp1 accepts a synthetic diacyl sulfolipid and transfers an acyl group regioselectively from one donor substrate molecule to a second acceptor molecule in two successive reactions to yield a tetraacylated product. Chp1 is fully active in vitro, but in M. tuberculosis, its function is potentiated by the previously identified sulfolipid transporter MmpL8. We also show that the integral membrane protein Sap and MmpL8 are both essential for sulfolipid transport. Finally, the lipase inhibitor tetrahydrolipstatin disrupts Chp1 activity in M. tuberculosis, suggesting an avenue for perturbing SL-1 biosynthesis in vivo. These data complete the SL-1 biosynthetic pathway and corroborate a model in which lipid biosynthesis and transmembrane transport are coupled at the membrane-cytosol interface through the activity of multiple proteins, possibly as a macromolecular complex.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.