4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815783/9781555814687_Chap04-1.gif /docserver/preview/fulltext/10.1128/9781555815783/9781555814687_Chap04-2.gif


This chapter focuses on the major metabolic steps and essential enzymatic players in the mycolic acid biosynthetic pathway, providing a historical perspective and highlighting the key advances of the last few years in this dynamic area. Information relative to the mycolic acid structure has been brought through the application of early and modern chemical techniques, in particular thin-layer chromatography (TLC), gas chromatography (GC), high-pressure liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The structures of mycolic acids of genera other than mycobacteria were found to be relatively simple in terms of chemical functions, being composed only of homologous series with various numbers of double bonds, up to 7 for some species. The pathway for synthesis of mycolic acids could be virtually divided into three major steps: (1) the synthesis and elongation of fatty acids to give precursors of both the α-branch and the very long meromycolic chain; (2) the elongation and introduction of functional modifications on the meromycolic chain; and (3) the condensation of two long-chain fatty acids, followed by a reduction to yield the mycolic acid specific motif. More recently, the involvement of the AccD4 carboxyltransferase in mycolic acid synthesis and its essentiality for mycobacterial survival have been demonstrated. Fatty acid synthase (FAS)-II has been shown to elongate medium-chain-length to C fatty acids to yield C-C acyl-ACPs in vitro, which are most likely the precursors of the very long-chain meromycolic acids.

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4

Key Concept Ranking

Type II Fatty Acid Synthase
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Chemical features of the mycolic acid structure. (A) Scheme of the pyrolytical cleavage of mycolic acid. R and R′ represent long hydrocarbon chains. (B) The C corynomycolic acid: 2-tetradecyl, 3-hydroxy octadecanoic acid from , where indicates the stereochemistry of carbons 2 and 3. The pyrolysis releases C acid and C “meroaldehyde.” (C) The dicyclopropanated mycolic acid (α-mycolate) from : the pyrolysis of the C homologue releases C acid and C “meroaldehyde.”

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Structures of representative types of mycolic acids and established/proposed functions of mycolic acid SAM-methyltransferases (MA-MTs)., representative species where these mycolate types occur are shown. The mycolate types displayed illustrate the functional groups of interest and therefore may not reflect the most abundant mycolate components. The indicate the configuration of unsaturations (double bonds or cyclopropanes) at the distal/proximal position. and , when known, refer to the stereochemistry of the asymmetric centers (i.e., carbons bearing the methyl, methoxyl or hydroxyl groups). Arrows point to the known or predicted action of the mycolic acid SAM-methyltransferases (MA-MTs) whose functions have been assigned by gene knockout or by heterologous expression (into parentheses).

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Model of the mycolic acid biosynthetic pathway in mycobacteria. The biosynthesis pathway of mycolic acids starts with the de novo synthesis and elongation of fatty acids operated by the mycobacterial FAS-I and FAS-II synthases, respectively. The FAS-II products have to undergo further elongation and modifications/decorations to produce the very long “meromycolic” chain precursors, whereas the carboxylation of acyl-CoAs (the FAS-I products) provides the activated alpha branch. Condensation of the latter with the activated “meromycolic” chain, followed by reduction, yields the mycolic acid with the characteristic motif.

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4.
Figure 4.

Mycobacterial (FAS-II) fatty acid synthesis. The names of the FAS-II orthologue proteins are indicated into parentheses. The malonyl-CoA:ACP transacylase (MtFabD) converts malonyl-CoA into malonyl-ACP. Cycles of fatty acid elongation are initiated by the condensation of acyl-CoAs (products of FAS-I) with malonyl-ACP catalyzed by β-ketoacyl-ACP synthase III (MtFabH). The second step in the elongation cycle is carried out by the β-ketoacyl-ACP reductase, MabA. The β-hydroxyacyl-ACP intermediate is dehydrated to form -2-enoyl-ACP. The final step in the elongation is catalyzed by the nicotinamide adenine dinucleotide (NADH)-dependent enoyl-ACP reductase (InhA). Subsequent rounds of elongation are initiated by the elongation condensing enzymes (KasA and KasB) whose substrate specificities govern the structure and distribution of fatty acid products.

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5.
Figure 5.

Model of the mycolic acid condensation. R1 and R2 represent long hydrocarbon chains, and X1 and X2 are the unknown intermediate acceptors. The fatty acid molecule bearing R1 is activated as acyl-adenylate (acyl-AMP) by FadD32 to yield the “meromycolate” chain. The other condensation substrate containing the R2 chain is activated by the acyl-CoA carboxylase complex to give the carboxylated intermediate at the origin of the α-branch. Condensation is catalyzed by Pks13, yielding a β-ketoester that gives, after reduction by the ketoacyl reductase CmrA, the mature mycolate.

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ahibo-Coffy, A.,, H. Aurelle,, C. Lacave,, J. C. Prome,, G. Puzo, and, A. Savagnac. 1978. Isolation, structural studies and chemical synthesis of a ‘palmitone lipid’ from Corynebacterium diphtheriae. Chem. Phys. Lipids 22:185195.
2. Alberts, A. W.,, S. G. Gordon, and, P. R. Vagelos. 1971. Acetyl CoA carboxylase: the purified transcarboxylase component. Proc. Natl. Acad. Sci. USA 68:12591263.
3. Asselineau, C., and, J. Asselineau. 1966. Stéréochimie de l’acide corynomycolique. Bull. Soc. Chim. France 6:19921999.
4. Asselineau, C.,, J. Asselineau,, G. Laneelle, and, M. A. Laneelle. 2002. The biosynthesis of mycolic acids by Mycobacteria: current and alternative hypotheses. Prog. Lipid Res. 41:501523.
5. Asselineau, C.,, C. Lacave,, H. Montrozier, and, J. C. Promé. 1970a. Relations structurales entre les acides mycoliques insaturés et les acides inférieurs insaturés synthétisés par Mycobacterium phlei. Implications métaboliques. Eur. J. Biochem. 14:406410.
6. Asselineau, C.,, G. Tocanne, and, J. F. Tocanne. 1970b. Stéréochimie des acides mycoliques. Bull. Soc. Chim. France 4:14551459.
7. Asselineau, J., and, E. Lederer. 1950. Structure of the mycolic acids of mycobacteria. Nature 166:782784.
8. Banerjee, A.,, E. Dubnau,, A. Quemard,, V. Balasubramanian,, K. S. Um,, T. Wilson,, D. Collins,, G. de Lisle, and, W. R., J. Jacobs. 1994. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263:227230.
9. Banerjee, A.,, M. Sugantino,, J. C. Sacchettini, and, W. R. J. Jacobs. 1998. The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance. Microbiology 144:26972704.
10. Bardou, F.,, A. Quemard,, M. A. Dupont,, C. Horn,, G. Marchal, and, M. Daffe. 1996. Effects of isoniazid on ultrastructure of Mycobacterium aurum and Mycobacterium tuberculosis and on production of secreted proteins. Antimicrob. Agents Chemother. 40:24592467.
11. Barry, C. E.,, III, R. E. Lee,, K. Mdluli,, A. E. Sampson,, B. G. Schroeder,, R. A. Slayden, and, Y. Yuan. 1998. Mycolic acids: structure, biosynthesis and physiological functions. Prog. Lipid Res. 37:143179.
12. Bateman, A.,, E. Birney,, R. Durbin,, S. R. Eddy,, K. L. Howe, and, E. L. Sonnhammer. 2000. The Pfam protein families database. Nucleic Acids Res. 28:263266.
13. Belisle, J. T.,, V. D. Vissa,, T. Sievert,, K. Takayama,, P. J. Brennan, and, G. S. Besra. 1997. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276:14201422.
14. Bhatt, A.,, N. Fujiwara,, K. Bhatt,, S. S. Gurcha,, L. Kremer,, B. Chen,, J. Chan,, S. A. Porcelli,, K. Kobayashi,, G. S. Besra, and, W. R. Jacobs, Jr. 2007. Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc. Natl. Acad. Sci. USA 104:51575162.
15. Bhatt, A.,, L. Kremer,, A. Z. Dai,, J. C. Sacchettini, and, W. R. Jacobs, Jr. 2005. Conditional depletion of KasA, a key enzyme of mycolic acid biosynthesis, leads to mycobacterial cell lysis. J. Bacteriol. 187:75967606.
16. Bloch, K. 1969. Enzymatic synthesis of monounsaturated fatty acids. Accounts Chem. Res. 2:193202.
17. Bloch, K. 1977. Control mechanisms for fatty acid synthesis in Mycobacterium smegmatis. Adv. Enzymol. 45:184.
18. Bloch, K., and, D. Vance. 1977. Control mechanisms in the synthesis of saturated fatty acids. Annu. Rev. Biochem. 46:263298.
19. Boissier, F.,, F. Bardou,, V. Guillet,, S. Uttenweiler-Joseph,, M. Daffe,, A. Quemard, and, L. Mourey. 2006. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 281:44344445.
20. Boshoff, H. I.,, T. G. Myers,, B. R. Copp,, M. R. McNeil,, M. A. Wilson, and, C. E. Barry III. 2004. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J. Biol. Chem. 279:4017440184.
21. Brand, S.,, K. Niehaus,, A. Puhler, and, J. Kalinowski. 2003. Identification and functional analysis of six mycolyltransferase genes of Corynebacterium glutamicum ATCC 13032: the genes cop1, cmt1, and cmt2 can replace each other in the synthesis of trehalose dicorynomycolate, a component of the mycolic acid layer of the cell envelope. Arch. Microbiol. 180:3344.
22. Brindley, N.,, S. Matsumura, and, K. Bloch. 1969. Mycobacterium phlei fatty acid synthetase-A bacterial multienzyme complex. Nature 224:666669.
23. Castell, A.,, P. Johansson,, T. Unge,, T. A. Jones, and, K. Backbro. 2005. Rv0216, a conserved hypothetical protein from Mycobacterium tuberculosis that is essential for bacterial survival during infection, has a double hotdog fold. Protein Sci. 14:18501862.
24. Chalut, C.,, L. Botella,, C. de Sousa-D’Auria,, C. Houssin, and, C. Guilhot. 2006. The nonredundant roles of two 4′-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc. Natl. Acad. Sci. USA 103:85118516.
25. Choi, K. H.,, L. Kremer,, G. S. Besra, and, C. O. Rock. 2000. Identification and substrate specificity of beta-ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J. Biol. Chem. 275:2820128207.
26. Chun, J.,, L. L. Blackall,, S. O. Kang,, Y. C. Hah, and, M. Goodfellow. 1997. A proposal to reclassify Nocardia pinensis Blackall et al. as Skermania piniformis gen. nov., comb. nov. Int. J. Syst. Bacteriol. 47:127131.
27. Cohen-Gonsaud, M.,, S. Ducasse,, F. Hoh,, D. Zerbib,, G. Labesse, and, A. Quemard. 2002. Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis. J. Mol. Biol. 320:249261.
28. Cole, S.,, K. Eiglmeier,, J. K. Parkhill,, N. R. Thomson,, P. R. Wheeler,, N. Honore,, T. Garnier,, C. Churcher,, D. Harris,, K. Mungall,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. M. Davies,, K. Devlin,, S. Duthoy,, T. Feltwell,, A. Fraser,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, C. Lacroix,, J. Maclean,, S. Moule,, L. Murphy,, K. Oliver,, M. A. Quail,, M. A. Rajandream,, K. M. Rutherford,, S. Rutter,, K. Seeger,, S. Simon,, M. Simmonds,, J. Skelton,, R. Squares,, S. Squares,, K. Stevens,, K. Taylor,, S. Whitehead,, J. R. Woodward, and, B. G. Barrell. 2001. Massive gene decay in the leprosy bacillus. Nature 409:10071011.
29. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels, and, B. G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537544.
30. Cronan, J. E., Jr., and, G. L. Waldrop. 2002. Multi-subunit acetyl-CoA carboxylases. Prog. Lipid Res. 41:407435.
31. Daffé, M. 1996. Structure de l’enveloppe de Mycobacterium tuberculosis. Med. Mal. Infect. 26:17.
32. Daffé, M. 2005. The cell envelope of corynebacteria, p. 121148. In L. Eggeling and, M. Bott (ed.), Handbook of Corynebacterium glutamicum. CRC Press, Boca Raton, FL.
33. Daffé, M., and, P. Draper. 1998. The envelope layer of mycobacteria with reference to their pathogenicity. Adv. Microb. Physiol. 39:131203.
34. Daffé, M.,, M. A. Laneelle,, C. Asselineau,, V. Levy-Frebault, and, H. L. David. 1983. Taxonomic value of mycobacterial fatty acids: proposal for a method of analysis. Ann. Microbiol. (Inst. Pasteur). 134:241256
35. Daffé, M.,, M. A. Laneelle,, G. Puzo, and, C. Asselineau. 1981. Acide mycolique epoxydique : un nouveau type d’acide mycolique. Tetrahedron Lett. 22:45154516.
36. Daniel, J.,, T. J. Oh,, C. M. Lee, and, P. E. Kolattukudy. 2007. AccD6, a Member of the Fas II Locus, is a functional carboxyltransferase subunit of the Acyl-CoA carboxylase in Mycobacterium tuberculosis. J. Bacteriol. 189:911917.
37. Datta, A. K., and, K. Takayama. 1993. Biosynthesis of a novel 3-oxo-2-tetradecyloctadecanoate-containing phospholipid by a cell-free extract of Corynebacterium diphtheriae. Biochim. Biophys. Acta 1169:135145.
38. Davidson, L. A.,, P. Draper, and, D. E. Minnikin. 1982. Studies on the mycolic acids from the walls of Mycobacterium microti. J. Gen. Microbiol. 128:823828.
39. De Briel, D.,, F. Couderc,, P. Riegel,, F. Jehl, and, R. Minck. 1992. High-performance liquid chromatography of corynomycolic acids as a tool in identification of Corynebacterium species and related organisms. J. Clin. Microbiol. 30:14071417.
40. De Sousa-D’Auria, C.,, R. Kacem,, V. Puech,, M. Tropis,, G. Leblon,, C. Houssin, and, M. Daffe. 2003. New insights into the biogenesis of the cell envelope of corynebacteria: identification and functional characterization of five new mycoloyltransferase genes in Corynebacterium glutamicum. FEMS Microbiol. Lett. 224:3544.
41. Dessen, A.,, A. Quemard,, J. S. Blanchard,, W. R. Jacobs, Jr., and, J. C. Sacchettini. 1995. Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science 267:16381641.
42. Diacovich, L.,, D. L. Mitchell,, H. Pham,, G. Gago,, M. M. Melgar,, C. Khosla,, H. Gramajo, and, S. C. Tsai. 2004. Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity. Biochemistry 43:1402714036.
43. Diacovich, L.,, S. Peiru,, D. Kurth,, E. Rodriguez,, F. Podesta,, C. Khosla, and, H. Gramajo. 2002. Kinetic and structural analysis of a new group of Acyl-CoA carboxylases found in Streptomyces coelicolor A3(2). J. Biol. Chem. 277:3122831236.
44. Dinadayala, P.,, F. Laval,, C. Raynaud,, A. Lemassu,, M. A. Laneelle,, G. Laneelle, and, M. Daffe. 2003. Tracking the putative biosynthetic precursors of oxygenated mycolates of Mycobacterium tuberculosis: structural analysis of fatty acids of a mutant strain devoid of methoxy- and keto-mycolates. J. Biol. Chem. 278:73107319.
45. Dubnau, E.,, J. Chan,, C. Raynaud,, V. P. Mohan,, M. A. Laneelle,, K. Yu,, A. Quemard,, I. Smith, and, M. Daffe. 2000. Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol. Microbiol. 36:630637.
46. Dubnau, E.,, M. A. Laneelle,, S. Soares,, A. Benichou,, T. Vaz,, D. Prome,, J. C. Prome,, M. Daffe, and, A. Quemard. 1997. Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto- and hydroxy-mycolic acids. Mol. Microbiol. 23:313322.
47. Dubnau, E.,, H. Marrakchi,, I. Smith,, M. Daffe, and, A. Quemard. 1998. Mutations in the cmaB gene are responsible for the absence of methoxymycolic acid in Mycobacterium bovis BCG Pasteur. Mol. Microbiol. 29:15261528.
48. Ducasse-Cabanot, S.,, M. Cohen-Gonsaud,, H. Marrakchi,, M. Nguyen,, D. Zerbib,, J. Bernadou,, M. Daffe,, G. Labesse, and, A. Quemard. 2004. In vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein reductase MabA by isoniazid. Antimicrob. Agents Chemother. 48:242249.
49. Etemadi, A. H. 1967. Structural and biogenetic correlations of mycolic acids in relation to the phylogenesis of various genera of Actinomycetales. Bull. Soc. Chim. Biol. (Paris) 49:695706.
50. Etemadi, A. H., and, J. Gasche. 1965. On the biogenetic origin of 2-eicosanol and 2-octadecanol of Mycobacterium avium. Bull. Soc. Chim. Biol. (Paris) 47:20952104.
51. Fernandes, N. D., and, P. E. Kolattukudy. 1996. Cloning, sequencing and characterization of a fatty acid synthase-encoding gene from Mycobacterium tuberculosis var. bovis BCG. Gene 170:9599.
52. Fraaije, M. W.,, N. M. Kamerbeek,, A. J. Heidekamp,, R. Fortin, and, D. B. Janssen. 2004. The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase. J. Biol. Chem. 279:33543360.
53. Fraaije, M. W.,, N. M. Kamerbeek,, W. J. van Berkel, and, D. B. Janssen. 2002. Identification of a Baeyer-Villiger monooxygenase sequence motif. FEBS Lett. 518:4347.
54. Fulco, A. J., and, Bloch. Bloch. 1964. Cofactor requirements for the formation of Delta-9-unsaturated fatty acids in Mycobacterium phlei. J. Biol. Chem. 239:993997.
55. Gago, G.,, D. Kurth,, L. Diacovich,, S. C. Tsai, and, H. Gramajo. 2006. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J. Bacteriol. 188:477486.
56. Gande, R.,, K. J. Gibson,, A. K. Brown,, K. Krumbach,, L. G. Dover,, H. Sahm,, S. Shioyama,, T. Oikawa,, G. S. Besra, and, L. Eggeling. 2004. Acyl-CoA carboxylases (accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycolic acid biosynthesis in Corynebacterineae such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J. Biol. Chem. 279:4484744857.
57. Gao, L. Y.,, F. Laval,, E. H. Lawson,, R. K. Groger,, A. Woodruff,, J. H. Morisaki,, J. S. Cox,, M. Daffe, and, E. J. Brown. 2003. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol. Microbiol. 49:15471563.
58. Gastambide-Odier, M., and, E. Lederer. 1960. Biosynthesis of corynomycolic acid from 2 molecules of palmitic acid. Biochem. Z. 333:285295.
59. George, K. M.,, Y. Yuan,, D. R. Sherman, and, C. E. Barry III. 1995. The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2. J. Biol. Chem. 270:2729227298.
60. Glickman, M. S. 2003. The mmaA2 gene of Mycobacterium tuberculosis encodes the distal cyclopropane synthase of the alpha-mycolic acid. J. Biol. Chem. 278:78447849.
61. Glickman, M. S.,, S. M. Cahill, and, W. R. Jacobs, Jr. 2001. The Mycobacterium tuberculosis cmaA2 gene encodes a mycolic acid trans-cyclopropane synthetase. J. Biol. Chem. 276:22282233.
62. Glickman, M. S.,, J. S. Cox, and, W. R. Jacobs, Jr. 2000. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell 5:717727.
63. Greenspan, M. D.,, C. H. Birge,, G. Powell,, W. S. Hancock, and, P. R. Vagelos. 1970. Enzyme specificity as a factor in regulation of fatty acid chain length in Escherichia coli. Science 170:12031204.
64. Grogan, D. W., and, J. E. Cronan, Jr. 1997. Cyclopropane ring formation in membrane lipids of bacteria. Microbiol. Mol. Biol. Rev. 61:429441.
65. Hazbon, M. H.,, M. Brimacombe,, M. Bobadilla del Valle,, M. Cavatore,, M. I. Guerrero,, M. Varma-Basil,, H. BillmanJacobe,, C. Lavender,, J. Fyfe,, L. Garcia-Garcia,, C. I. Leon,, M. Bose,, F. Chaves,, M. Murray,, K. D. Eisenach,, J. SifuentesOsornio,, M. D. Cave,, A. Ponce de Leon, and, D. Alland. 2006. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 50:26402649.
66. Holton, S. J.,, S. King-Scott,, A. N. Eddine,, S. H. Kaufmann, and, M. Wilmanns. 2006. Structural diversity in the six-fold redundant set of acyl-CoA carboxyltransferases in Mycobacterium tuberculosis. FEBS Lett. 580:68986902.
67. Huang, C. C.,, C. V. Smith,, M. S. Glickman,, W. R. Jacobs, Jr., and, J. C. Sacchettini. 2002. Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis. J. Biol. Chem. 277:1155911569.
68. Huang, Y.,, J. Ge,, Y. Yao,, Q. Wang,, H. Shen, and, H. Wang. 2006a. Characterization and site-directed mutagenesis of the putative novel acyl carrier protein Rv0033 and Rv1344 from Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 342:618624.
69. Huang, Y. S.,, J. Ge,, H. M. Zhang,, J. Q. Lei,, X. L. Zhang, and, H. H. Wang. 2006b. Purification and characterization of the Mycobacterium tuberculosis FabD2, a novel malonyl-CoA: AcpM transacylase of fatty acid synthase. Protein Expr. Purif. 45:393399.
70. Hughes, M. A.,, J. C. Silva,, S. J. Geromanos, and, C. A. Townsend. 2006. Quantitative proteomic analysis of drug-induced changes in mycobacteria. J. Proteome Res. 5:5463.
71. Kacem, R.,, C. De Sousa-D’Auria,, M. Tropis,, M. Chami,, P. Gounon,, G. Leblon,, C. Houssin, and, M. Daffe. 2004. Importance of mycoloyltransferases on the physiology of Corynebacterium glutamicum. Microbiology 150:7384.
72. Kastaniotis, A. J.,, K. J. Autio,, R. T. Sormunen, and, J. K. Hiltunen. 2004. Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essential for mitochondrial function and morphology. Mol. Microbiol. 53:14071421.
73. Kikuchi, S., and, T. Kusaka. 1982. New malonyl-CoA-dependent fatty acid elongation system in Mycobacterium smegmatis. J. Biochem. (Tokyo) 92:839844.
74. Kikuchi, S.,, T. Takeuchi,, M. Yasui,, T. Kusaka, and, P. E. Kolattukudy. 1989. A very long-chain fatty acid elongation system in Mycobacterium avium and a possible mode of action of isoniazid on the system. Agric. Biol. Chem. 53:16891698.
75. Kremer, L.,, L. G. Dover,, S. Carrere,, K. M. Nampoothiri,, S. Lesjean,, A. K. Brown,, P. J. Brennan,, D. E. Minnikin,, C. Locht, and, G. S. Besra. 2002. Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis. Biochem. J. 364:423430.
76. Kremer, L.,, K. M. Nampoothiri,, S. Lesjean,, L. G. Dover,, S. Graham,, J. Betts,, P. J. Brennan,, D. E. Minnikin,, C. Locht, and, G. S. Besra. 2001. Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. J. Biol. Chem. 276:2796727974.
77. Labesse, G.,, A. Vidal-Cros,, J. Chomilier,, M. Gaudry, and, J.-P. Mornon. 1994. Structural comparisons lead to the definition of a new superfamily of NAD(P)(H)-accepting oxidoreductases: the single-domain reductases/epimerases/dehydrogenases (the RED family). Biochem. J. 304:9599.
78. Lacave, C.,, M. A. Laneelle,, M. Daffe,, H. Montrozier,, M. P. Rols, and, C. Asselineau. 1987. Structural and metabolic study of the mycolic acids of Mycobacterium fortuitum. Eur. J. Biochem. 163:369378.
79. Lai, C. Y., and, J. E. Cronan. 2003. Beta-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis. J. Biol. Chem. 278:5149451503.
80. Lai, C. Y., and, J. E. Cronan. 2004. Isolation and characterization of beta-ketoacyl-acyl carrier protein reductase (fabG) mutants of Escherichia coli and Salmonella enterica serovar Typhimurium. J. Bacteriol. 186:18691878.
81. Laneelle, M. A., and, G. Laneelle. 1970. Structure of mycolic acids and an intermediate in the biosynthesis of dicarboxylic mycolic acids. Eur. J. Biochem. 12:296300.
82. Laval, F.,, R. Haites,, F. Movahedzadeh,, A. Lemassu,, C. Y. Wong,, N. Stoker,, H. Billman-Jacobe, and, M. Daffé. 2007. Investigating the function of the putative mycolic-acid methyltransferase UmaA: divergence between the Mycobacterium smegmatis and Mycobacterium tuberculosis proteins. J. Biol. Chem., in press.
83. Laval, F., M., A. Laneelle,, C. Deon,, B. Monsarrat, and, M. Daffe. 2001. Accurate molecular mass determination of mycolic acids by MALDI-TOF mass spectrometry. Anal. Chem. 73:45374544.
84. Lea-Smith, D. J.,, J. S. Pyke,, D. Tull,, M. J. McConville,, R. L. Coppel, and, P. K. Crellin. 2007. The reductase that catalyzes mycolic motif synthesis is required for efficient attachment of mycolic acids to arabinogalactan. J. Biol. Chem. 282:1100011008.
85. Lederer, E. 1969. Some problems concerning biological C-alkylation reactions and phytosterol biosynthesis. Q. Rev. Chem. Soc. 23:453481.
86. Lee, R.,, J. Armour,, K. Takayama,, P. Brennan, and, G. Besra. 1997. Mycolic acid biosynthesis: Definition and targeting of the Claisen condensation step. Biochim. Biophys. Acta 1346:275284.
87. Lin, T. W.,, M. M. Melgar,, D. Kurth,, S. J. Swamidass,, J. Purdon,, T. Tseng,, G. Gago,, P. Baldi,, H. Gramajo, and, S. C. Tsai. 2006. Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 103:30723077.
88. Marrakchi, H.,, K. H. Choi, and, C. O. Rock. 2002a. A new mechanism for anaerobic unsaturated fatty acid formation in Streptococcus pneumoniae. J. Biol. Chem. 277:4480944816.
89. Marrakchi, H.,, S. Ducasse,, G. Labesse,, H. Montrozier,, E. Margeat,, L. Emorine,, X. Charpentier,, M. Daffe, and, A. Quemard. 2002b. MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology 148:951960.
90. Marrakchi, H.,, G. Laneelle, and, A. Quemard. 2000. InhA, a target of the antituberculous drug isoniazid, is involved in a mycobacterial fatty acid elongation system, FAS-II. Microbiology 146:289296.
91. Marrakchi, H.,, Y. M. Zhang, and, C. O. Rock. 2002c. Mechanistic diversity and regulation of Type II fatty acid synthesis. Biochem. Soc. Trans. 30:10501055.
92. McNeil, M.,, M. Daffe, and, P. J. Brennan. 1991. Location of the mycolyl ester substituents in the cell walls of mycobacteria. J. Biol. Chem. 266:1321713223.
93. Minnikin, D. E.,, S. M. Minnikin,, G. Dobson,, M. Goodfellow,, F. Portaels,, L. van den Breen, and, D. Sesardic. 1983. Mycolic acid patterns of four vaccine strains of Mycobacterium bovis BCG. J. Gen. Microbiol. 129:889891.
94. Minnikin, D. E.,, S. M. Minnikin, and, M. Goodfellow. 1982. The oxygenated mycolic acids of Mycobacterium fortiutum, M. arcinogenes and M. senegalense. Biochim. Biophys. Acta 712:616620.
95. Molle, V.,, A. K. Brown,, G. S. Besra,, A. J. Cozzone, and, L. Kremer. 2006. The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation. J. Biol. Chem. 281:3009430103.
96. Nishiuchi, Y.,, T. Baba,, H. H. Hotta, and, I. Yano. 1999. Mycolic acid analysis in Nocardia species. The mycolic acid compositions of Nocardia asteroides, N. farcinica, and N. nova. J. Microbiol. Methods 37:111122.
97. Nishiuchi, Y.,, T. Baba, and, I. Yano. 2000. Mycolic acids from Rhodococcus, Gordonia, and Dietzia. J. Microbiol. Methods 40:19.
98. Odriozola, J. M.,, J. A. Ramos, and, K. Bloch. 1977. Fatty acid synthetase activity in Mycobacterium smegmatis. Characterization of the acyl carrier protein-dependent elongating system. Biochim. Biophys. Acta 488:207217.
99. Oh, T. J.,, J. Daniel,, H. J. Kim,, T. D. Sirakova, and, P. E. Kolattukudy. 2006. Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv. J. Biol. Chem. 281:38993908.
100. Parish, T.,, G. Roberts,, F. Laval,, M. Schaeffer,, M. Daffé, and, K. Duncan. 2007. Functional complementation of the essential gene fabG1 of Mycobacterium tuberculosis by Mycobacterium smegmatis fabG but not Escherichia coli fabG. J. Bacteriol. 189:37213728.
101. Phetsuksiri, B.,, M. Jackson,, H. Scherman,, M. McNeil,, G. S. Besra,, A. R. Baulard,, R. A. Slayden,, A. E. DeBarber,, C. E. Barry III,, M. S. Baird,, D. C. Crick, and, P. J. Brennan. 2003. Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis. J. Biol. Chem. 278:5312353130.
102. Portevin, D.,, C. De Sousa-D’Auria,, C. Houssin,, C. Grimaldi,, M. Chami,, M. Daffe, and, C. Guilhot. 2004. A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms. Proc. Natl. Acad. Sci. USA 101:314319.
103. Portevin, D.,, C. de Sousa-D’Auria,, H. Montrozier,, C. Houssin,, A. Stella,, M. A. Laneelle,, F. Bardou,, C. Guilhot, and, M. Daffe. 2005. The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: identification of the carboxylation product and determination of the acyl-CoA carboxylase components. J. Biol. Chem. 280:88628874.
104. Prome, J. C.,, R. W. Walker, and, C. Lacave. 1974. Condensation of two molecules of palmitic acid in Corynebacterium diphtheriae: formation of a beta-keto ester of trehalose. C. R. Acad. Sci. Paris C 278:10651068.
105. Puech, V.,, N. Bayan,, K. Salim,, G. Leblon, and, M. Daffe. 2000. Characterization of the in vivo acceptors of the mycoloyl residues transferred by the corynebacterial PS1 and the related mycobacterial antigens 85. Mol. Microbiol. 35:10261041.
106. Puech, V.,, C. Guilhot,, E. Perez,, M. Tropis,, L. Y. Armitige,, B. Gicquel, and, M. Daffe. 2002. Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis. Mol. Microbiol. 44:11091122.
107. Quémard, A.,, G. Laneelle, and, C. Lacave. 1992. Mycolic acid synthesis: a target for ethionamide in mycobacteria? Antimicrob. Agents Chemother. 36:13161321.
108. Quémard, A.,, J. C. Sacchettini,, A. Dessen,, C. Vilcheze,, R. Bittman,, W. R. Jacobs, Jr., and, J. S. Blanchard. 1995. Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis. Biochemistry 34:82358241.
109. Qureshi, N.,, N. Sathyamoorthy, and, K. Takayama. 1984. Biosynthesis of C30 to C56 fatty acids by an extract of Mycobacterium tuberculosis H37Ra. J. Bacteriol. 157:4652.
110. Radmacher, E.,, L. J. Alderwick,, G. S. Besra,, A. K. Brown,, K. J. Gibson,, H. Sahm, and, L. Eggeling. 2005. Two functional FAS-I type fatty acid synthases in Corynebacterium glutamicum. Microbiology 151:24212427.
111. Rafidinarivo, E.,, J. C. Prome, and, V. Levy-Frebault. 1985. New kinds of unsaturated mycolic acids from Mycobacterium fallax sp. nov. Chem. Phys. Lipids 36:215228.
112. Rainey, F. A.,, S. Klatte,, R. M. Kroppenstedt, and, E. Stackebrandt. 1995. Dietzia, a new genus including Dietzia maris comb. nov., formerly Rhodococcus maris. Int. J. Syst. Bacteriol. 45:3236.
113. Rao, V.,, N. Fujiwara,, S. A. Porcelli, and, M. S. Glickman. 2005. Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule. J. Exp. Med. 201:535543.
114. Rao, V.,, F. Gao,, B. Chen,, W. R. Jacobs, Jr., and, M. S. Glickman. 2006. Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence. J. Clin. Investig. 116:16601667.
115. Rehm, H. J., and, I. Reiff. 1981. Mechanisms and occurence of microbial oxidation of long-chain alkanes. Adv. Biochem. Eng. 19:175215.
116. Revill, W. P.,, M. J. Bibb, and, D. A. Hopwood. 1996. Relationships between fatty acid and polyketide synthases from Streptomyces coelicolor A3(2): characterization of the fatty acid synthase acyl carrier protein. J. Bacteriol. 178:56605667.
117. Rock, C. O., and, J. E. Cronan. 1996. Escherichia coli as a model for the regulation of dissociable (type II) fatty acid biosynthesis. Biochim. Biophys. Acta 1302:116.
118. Sacco, E.,, V. Legendre,, F. Laval,, D. Zerbib,, H. Montrozier,, N. Eynard,, C. Guilhot,, M. Daffe, and, A. Quemard. 2007a. Rv3389c from Mycobacterium tuberculosis, a member of the (R)-specific hydratase/dehydratase family. Biochim. Biophys. Acta 1774:303311.
119. Sacco, E.,, A. Suarez Covarrubias,, H. M. O’Hare,, P. Carroll,, N. Eynard,, T. A. Jones,, T. Parish,, M. Daffé,, K. Bäckbro, and, A. Quémard. 2007b. The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 104:1462814633.
120. Sassetti, C. M.,, D. H. Boyd, and, E. J. Rubin. 2003. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48:7784.
121. Sassetti, C. M., and, E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA 100:1298912994.
122. Schaeffer, M. L.,, G. Agnihotri,, H. Kallender,, P. J. Brennan, and, J. T. Lonsdale. 2001a. Expression, purification, and characterization of the Mycobacterium tuberculosis acyl carrier protein, AcpM. Biochim. Biophys. Acta 1532:6778.
123. Schaeffer, M. L.,, G. Agnihotri,, C. Volker,, H. Kallender,, P. J. Brennan, and, J. T. Lonsdale. 2001b. Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB. J. Biol. Chem. 276:4702947037.
124. Shimakata, T.,, Y. Fujita, and, T. Kusaka. 1977. Acetyl-CoA-dependent elongation of fatty acids in Mycobacterium smegmatis. J. Biochem. (Tokyo) 82:725732.
125. Shimakata, T.,, M. Iwaki, and, T. Kusaka. 1984. In vitro synthesis of mycolic acids by the fluffy layer fraction of Bacterionema matruchotii. Arch. Biochem. Biophys. 229:329339.
126. Shimakata, T.,, K. Tsubokura,, T. Kusaka, and, K. Shizukuishi. 1985. Mass-spectrometric identification of trehalose 6-monomycolate synthesized by the cell-free system of Bacterionema matruchotii. Arch. Biochem. Biophys. 238:497508.
127. Slayden, R. A., and, C. E. Barry III. 2002. The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis (Edinburgh) 82:149160.
128. Takayama, K., and, N. Qureshi. 1978. Isolation and characterization of monounsaturated long chain fatty acids of Mycobacterium tuberculosis. Lipids 13:575579.
129. Takayama, K.,, C. Wang, and, G. S. Besra. 2005. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 18:81101.
130. Takayama, K.,, L. Wang, and, H. L. David. 1972. Effect of isoniazid on the in vivo mycolic acid synthesis, cell growth, and viability of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2:2935.
131. Thierry, D.,, V. Vincent,, F. Clement, and, J. L. Guesdon. 1993. Isolation of specific DNA fragments of Mycobacterium avium and their possible use in diagnosis. J. Clin. Microbiol. 31:10481054.
132. Tomiyasu, I., and, I. Yano. 1984. Isonicotinic acid hydrazide induced changes and inhibition in mycolic acid synthesis in Nocardia and related taxa. Arch. Microbiol. 137:316323.
133. Tong, L. 2005. Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell Mol. Life Sci. 62:17841803.
134. Toriyama, S.,, S. Izaizumi,, I. Tomiyasu,, M. Masui, and, I. Yano. 1982. Incorporation of 18O into long-chain secondary alkohols derived from ester mycolic acids in Mycobacterium phlei. Biochim. Biophys. Acta 712:427429.
135. Trivedi, O. A.,, P. Arora,, V. Sridharan,, R. Tickoo,, D. Mohanty, and, R. S. Gokhale. 2004. Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature 428:441445.
136. Tropis, M.,, X. Meniche,, A. Wolf,, H. Gebhardt,, S. Strelkov,, M. Chami,, D. Schomburg,, R. Kramer,, S. Morbach, and, M. Daffe. 2005. The crucial role of trehalose and structurally related oligosaccharides in the biosynthesis and transfer of mycolic acids in Corynebacterineae. J. Biol. Chem. 280:2657326585.
137. Veyron-Churlet, R.,, O. Guerrini,, L. Mourey,, M. Daffe, and, D. Zerbib. 2004. Protein-protein interactions within the Fatty Acid Synthase-II system of Mycobacterium tuberculosis are essential for mycobacterial viability. Mol. Microbiol. 54:11611172.
138. Vilcheze, C.,, H. Morbidoni,, T. Weisbrod,, H. Iwamoto,, M. Kuo,, J. Sacchattini, and, W. R. Jacobs, Jr. 2000. Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis. J. Bacteriol. 182:40594067.
139. Vilcheze, C.,, F. Wang,, M. Arai,, M. H. Hazbon,, R. Colangeli,, L. Kremer,, T. R. Weisbrod,, D. Alland,, J. C. Sacchettini, and, W. R. Jacobs, Jr. 2006. Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nat. Med. 12:10271029.
140. Walker, R. W.,, J. C. Promé, and, C. Lacave. 1973. Biosynthesis of mycolic acids. Formation of a C32-β-ketoester from palmitic acid in a cell-free system of Corynebacterium diphteriae. Biochem. Biophys. Acta 326:5262.
141. Watanabe, M.,, Y. Aoyagi,, M. Ridell, and, D. E. Minnikin. 2001. Separation and characterization of individual mycolic acids in representative mycobacteria. Microbiology 147:18251837.
142. Wheeler, P. R.,, K. Bulmer, and, C. Ratledge. 1990. Enzymes for biosynthesis de novo and elongation of fatty acids in mycobacteria grown in host cells: is Mycobacterium leprae competent in fatty acid biosynthesis? J. Gen. Microbiol. 136:211217.
143. Wong, M. Y., and, G. R. Gray. 1979. Structures of the homologous series of monoalkene mycolic acids from Mycobacterium smegmatis. J. Biol. Chem. 254:57415744.
144. Yang, J. K.,, H. J. Yoon,, H. J. Ahn,, B. I. Lee,, S. H. Cho,, G. S. Waldo,, M. S. Park, and, S. W. Suh. 2002. Crystallization and preliminary X-ray crystallographic analysis of the Rv2002 gene product from Mycobacterium tuberculosis, a beta-ketoacyl carrier protein reductase homologue. Acta Crystallogr. D 58:303305.
145. Yuan, Y., and, C. E. Barry. 1996. A common mechanism for the biosynthesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 93:1282812833.
146. Yuan, Y.,, D. C. Crane,, J. M. Musser,, S. Sreevatsan, and, C. E. Barry III. 1997. MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis. J. Biol. Chem. 272:1004110049.
147. Yuan, Y.,, R. E. Lee,, G. S. Besra,, J. T. Belisle, and, C. E. Barry III. 1995. Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 92:66306634.
148. Yuan, Y.,, D. Mead,, B. G. Schroeder,, Y. Zhu, and, C. E. Barry III. 1998a. The biosynthesis of mycolic acids in Mycobacterium tuberculosis. Enzymatic methyl(ene) transfer to acyl carrier protein bound meromycolic acid in vitro. J. Biol. Chem. 273:2128221290.
149. Yuan, Y.,, Y. Zhu,, D. D. Crane, and, C. E. Barry III. 1998b. The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Mol. Microbiol. 29:14491458.
150. Zhang, Y., and, J. E. Cronan, Jr. 1996. Polar allele duplication for transcriptional analysis of consecutive essential genes: application to a cluster of Escherichia coli fatty acid biosynthetic genes. J. Bacteriol. 178:36143620.
151. Zhang, Y. M.,, H. Marrakchi,, S. W. White, and, C. O. Rock. 2003. The application of computational methods to explore the diversity and structure of bacterial fatty acid synthase. J. Lipid Res. 44:110.
152. Zimhony, O.,, J. S. Cox,, J. T. Welch,, C. Vilcheze, and, W. R. J. Jacobs. 2000. Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat. Med. 9:10431047.


Generic image for table
Table 1.

genes involved in fatty acid and mycolic acid synthesis

Citation: Marrakchi H, Bardou F, Lanéelle M, Daffé M. 2008. 4 A Comprehensive Overview of Mycolic Acid Structure and Biosynthesis, p 41-61. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch4

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error