Mycolic Acids: Structures, Biosynthesis, and Beyond
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Mycolic acids are major and specific lipid components of the mycobacterial cell envelope and are essential for the survival of members of the genus Mycobacterium that contains the causative agents of both tuberculosis and leprosy. In the alarming context of the emergence of multidrug-resistant, extremely drug-resistant, and totally drug-resistant tuberculosis, understanding the biosynthesis of these critical determinants of the mycobacterial physiology is an important goal to achieve, because it may open an avenue for the development of novel antimycobacterial agents. This review focuses on the chemistry, structures, and known inhibitors of mycolic acids and describes progress in deciphering the mycolic acid biosynthetic pathway. The functional and key biological roles of these molecules are also discussed, providing a historical perspective in this dynamic area.
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The α-chain and the first several carbons of the meromycolate are synthesized by FAS-I enzymes, and FAS-II enzymes then elongate these chains into the meromycolates.
“The α-chain and the first several carbons of the meromycolate are synthesized by fatty acid synthase I (FAS-I) enzymes. FAS-II enzymes then elongate these chains into the meromycolates.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [21]
The MA Biosynthesis and Synthesis of the Alpha-Alkyl Branch sections state that FAS-I produces the α-branch precursor and fatty acids that FAS-II elongates toward meromycolic chains. However, Concluding Remarks and Perspectives says FAS-II elongation to full-length meromycolates in vivo has not been formally demonstrated, so the claim presents the final step more definitively than the source does. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe modified meromycolates and the α-chains are combined to make mycolic acids before export.
“The modified meromycolates and the α-chains are combined to make mycolic acids before export”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [21]
The Condensation Enzymes section says the meromycolic chain and α-branch are joined in the final condensation step, and the Concluding Remarks say mycolic acids are then transported to the mycomembrane. But the Concluding Remarks also say it remains unproven whether the meromycolic modifications occur before that step or in completed mycolic acids, so describing the meromycolates as already modified overstates the source. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMycolic acids consist of 2-alkyl, 3-hydroxy long-chain fatty acids, in which the α-chain is saturated and 22-26 carbons long, and the meromycolate is 42-62 carbons long.
“Mycolic acids consist of 2-alkyl, 3-hydroxy long-chain fatty acids, in which the lipid at the 2 position, called the α-chain, is saturated and 22–26 carbons long. The lipid on the 3-hydroxyl, the meromycolate, is 42–62 carbons long”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [21]
The MA Biosynthesis section describes the 2-alkyl, 3-hydroxy mycolic motif and identifies a C24–C26 α branch in mycobacterial mycolic acids. Structure and Diversity of MAs reports C22–C24 fatty acids for most Mycobacterium species, with C26 prominent in some, but also describes substantial variation across genera. The cited passages do not establish that every α-chain is saturated or that meromycolate chains are uniformly 42–62 carbons long; page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe mycomembrane outer leaflet is composed mostly of mycolic acids, which can be free or attached to trehalose to make TMM or TDM.
“Its outer leaflet is composed mostly of mycolic acids, which can be free or attached to trehalose sugar to make trehalose mono mycolate (TMM) or trehalose dimycolate (TDM)21”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [21]
The Introduction says mycolic acids occur in unbound and trehalose-ester forms and participate in the mycomembrane’s two leaflets. The Figure 1 description in the MA Biosynthesis section includes TMM and TDM among membrane lipids, but it does not say the outer leaflet is composed mostly of mycolic acids; it also lists other glycolipids and phospholipids. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredModifications of mycolic acids include desaturations, cis or trans cyclopropanations, and addition of hydroxy, keto and methoxy groups.
“Modifications of mycolic acids include desaturations and either cis or trans cyclopropana- tions that bend the meromycolate chain back on itself, as well as addition of hydroxy, keto and methoxy groups oriented towards the polar edge of the membrane21.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [21]
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Cites
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., et al. (1998) · Nature · doi:10.1038/31159 · Cited by 7,847 · see citing works
Banerjee, A., Dubnau, E., Quemard, A., Balasubramanian, V., Um, K. S., Wilson, T., Collins, D., de Lisle, G., & Jacobs, W. R. (1994) · Science · doi:10.1126/science.8284673 · Cited by 1,389 · see citing works
Hoffmann, C., Leis, A., Niederweis, M., Plitzko, J. M., & Engelhardt, H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709530105 · Cited by 596 · see citing works
Rao, V. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27335 · Cited by 200 · see citing works
Puech, V., Guilhot, C., Perez, E., Tropis, M., Armitige, L. Y., Gicquel, B., & Daffé, M. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02953.x · Cited by 121 · see citing works
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Flagged first, then by citations
Research works printed but not linked: 16
- Chalut, C., Botella, L., de Sousa-D'Auria, C., Houssin, C., and Guilhot, C. (2006). The nonredundant roles of two 4 0 -phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc. Natl. Acad. Sci. USA 103, 8511- 8516.
- Daffe ´, M. (2005). The Cell Envelope of Corynebacteria. In Handbook of Cory- nebacterium glutamicum, L. Eggeling and M. Bott, eds. (Boca Raton: CRC Press), pp. 121-148.
- Goren, M.B., and Brennan, P.J. (1979). Mycobacterial lipids: chemistry and biological activities. In Tuberculosis, G.P. Youmans, ed. (Philadelphia: The W. B. Saunders), pp. 63-193.
- Guilhot, C., Chalut, C., and Daffe ´, M. (2008). Biosynthesis and roles of phenolic glycolipids and related molecules in M. tuberculosis. In The Mycobacterial Cell Envelope, M. Daffe ´and J.M. Reyrat, eds. (Washington, DC: ASM Press), pp. 273-289.
- Hunter, R.L., Armitige, L., Jagannath, C., and Actor, J.K. (2009). TB research at UT-Houston-a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis. Tuberculosis (Edinb.) 89 (Suppl 1 ), S18-S25.
- Lin, T.W., Melgar, M.M., Kurth, D., Swamidass, S.J., Purdon, J., Tseng, T., Gago, G., Baldi, P., Gramajo, H., and Tsai, S.C. (2006). Structure-based inhib- itor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 103, 3072-3077.
- Liu, J., Rosenberg, E.Y., and Nikaido, H. (1995). Fluidity of the lipid domain of cell wall from Mycobacterium chelonae. Proc. Natl. Acad. Sci. USA 92, 11254- 11258.
- Marrakchi, H., Zhang, Y.M., and Rock, C.O. (2002b). Mechanistic diversity and regulation of Type II fatty acid synthesis. Biochem. Soc. Trans. 30, 1050-1055.
- Marrakchi, H., Bardou, F., Lane ´elle, M., and Daffe ´, M. (2008). A comprehensive overview of mycolic acid structure and biosynthesis. In The Mycobacterial Cell Envelope, M. Daffe ´and J.M. Reyrat, eds. (Washington, DC: ASM Press), pp. 41-62.
- Minnikin, D.E. (1982). Lipids: complex lipids, their chemistry, biosynthesis and roles. In The Biology of the Mycobacteria, Volume 1 (London: Academic Press), pp. 95-184.
- Portevin, D., de Sousa-D'Auria, C., Houssin, C., Grimaldi, C., Chami, M., Daffe ´, M., and Guilhot, C. (2004). A polyketide synthase catalyzes the last condensa- tion step of mycolic acid biosynthesis in Mycobacteria and related organisms. Proc. Natl. Acad. Sci. USA 101, 314-319.
- Sacco, E., Covarrubias, A.S., O'Hare, H.M., Carroll, P., Eynard, N., Jones, T.A., Parish, T., Daffe ´, M., Ba ¨ckbro, K., and Que ´mard, A. (2007). The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 104, 14628-14633.
- Sassetti, C.M., Boyd, D.H., and Rubin, E.J. (2001). Comprehensive identifica- tion of conditionally essential genes in mycobacteria. Proc. Natl. Acad. Sci. USA 98, 12712-12717.
- Stanley, S.A., Kawate, T., Iwase, N., Shimizu, M., Clatworthy, A.E., Kazyan- skaya, E., Sacchettini, J.C., Ioerger, T.R., Siddiqi, N.A., Minami, S., et al. (2013). Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacte- rium tuberculosis by targeting FadD32. Proc. Natl. Acad. Sci. USA 110, 11565- 11570.
- Yuan, Y., Lee, R.E., Besra, G.S., Belisle, J.T., and Barry, C.E., 3rd. (1995). Iden- tification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 92, 6630- 6634.
- Yuan, Y., and Barry, C.E., 3rd. (1996). A common mechanism for the biosyn- thesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tubercu- losis. Proc. Natl. Acad. Sci. USA 93, 12828-12833.
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Donia, M. S., & Fischbach, M. A. (2015) · Science · doi:10.1126/science.1254766 · Cited by 760 · see citing works
The mycobacterial cell envelope — a moving target
Dulberger, C. L., Rubin, E. J., & Boutte, C. C. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0273-7 · Cited by 365 · see citing works
Cell Walls and Membranes of Actinobacteria
Rahlwes, K. C., Sparks, I. L., & Morita, Y. S. (2019) · Subcellular Biochemistry · doi:10.1007/978-3-030-18768-2_13 · Cited by 65 · see citing works
Transport of outer membrane lipids in mycobacteria
Touchette, M. H., & Seeliger, J. C. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.01.005 · Cited by 33 · see citing works
- Authors
- Marrakchi, H., Lanéelle, M.-A., & Daffé, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Daffé, Mamadou
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 21
- Issue
- 1
- Pages
- 67-85
- ISSN
- 1074-5521 (ISSN-L)
- OpenAlex
- W2046928094
- Cited by
- 623
- References
- 5
- Citations by year
- 2026: 53 · 2025: 63 · 2024: 50 · 2023: 55 · 2022: 62 · 2021: 60 · 2020: 70 · 2019: 58 · 2018: 37 · 2017: 46 · 2016: 34 · 2015: 23 · 2014: 12
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- mycolic acids, mycolic acid biosynthesis, mycobacterial cell envelope, Mycobacterium, tuberculosis, leprosy, multidrug-resistant tuberculosis, totally drug-resistant tuberculosis, antimycobacterial agents, biosynthetic pathway
- MeSH terms
- Antitubercular Agents, Humans, Molecular Conformation, Mycobacterium, Mycolic Acids, Virulence
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