The Mycobacterium tuberculosis FAS-II condensing enzymes: Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development

Molecular Microbiology

Volumn 64, Issue 6, 2007, Pages 1442-1454

  Bhatt, Apoorva ^a   Molle, Virginie ^b   Besra, Gurdyal S ^a   Jacobs Jr , William R ^c   Kremer, Laurent ^d  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b INSTITUT DE BIOLOGIE ET CHIMIE DES PROTÉINES   (France)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^d UNIVERSITÉ DE MONTPELLIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID SYNTHASE; FATTY ACID SYNTHASE II; MYCOLIC ACID; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG;

BACTERIAL CELL WALL; BACTERIAL VIRULENCE; BIOFILM; CATALYSIS; CHEMICAL BOND; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME LOCALIZATION; ENZYME PHOSPHORYLATION; FATTY ACID SYNTHESIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; SHORT SURVEY; TUBERCULOSIS;

ANIMALS; ANTITUBERCULAR AGENTS; ENZYME INHIBITORS; FATTY ACID SYNTHETASE COMPLEX; HUMANS; MICE; MYCOBACTERIUM TUBERCULOSIS; MYCOLIC ACIDS; TUBERCULOSIS; VIRULENCE;

CORYNEBACTERINEAE; MYCOBACTERIUM TUBERCULOSIS;

EID: 34250198660     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/j.1365-2958.2007.05761.x     Document Type: Short Survey

References (66)

1. Argyrou, A., Jin, L., Siconilfi-Baez, L., Angeletti, R.H. Blanchard, J.S. (2006) Proteome-wide profiling of isoniazid targets in Mycobacterium tuberculosis. Biochemistry 45 : 13947 13953.
2. Av-Gay, Y. Everett, M. (2000) The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis. Trends Microbiol 8 : 238 244.
3. Banerjee, A., Dubnau, E., Quemard, A., Balasubramanian, V., Um, K.S., Wilson, T., et al. (1994) inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263 : 227 230.
4. Bhatt, A., Kremer, L., Dai, A.Z., Sacchettini, J.C. Jacobs, W.R., Jr. (2005) Conditional depletion of KasA, a key enzyme of mycolic acid biosynthesis, leads to mycobacterial cell lysis. J Bacteriol 187 : 7596 7606.
5. Bhatt, A., Fujiwara, N., Bhatt, K., Gurcha, S.S., Kremer, L., Chen, B., et al. (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 : 5157 5162.
6. Brennan, P.J. Nikaido, H. (1995) The envelope of mycobacteria. Annu Rev Biochem 64 : 29 63.
7. Brown, A.K., Sridharan, S., Kremer, L., Lindenberg, S., Dover, L.G., Sacchettini, J.C. Besra, G.S. (2005) Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mtFabH: factors influencing catalysis and substrate specificity. J Biol Chem 280 : 32539 32547.
8. Choi, K.H., Kremer, L., Besra, G.S. Rock, C.O. (2000) Identification and substrate specificity of beta-ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J Biol Chem 275 : 28201 28207.
9. Colas, P., Cohen, B., Jessen, T., Grishina, I., McCoy, J. Brent, R. (1996) Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature 380 : 548 550.
10. Cole, S.T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 : 537 544.
11. Daffe, M. Draper, P. (1998) The envelope layers of mycobacteria with reference to their pathogenicity. Adv Microb Physiol 39 : 131 203.
12. Dubnau, E., Chan, J., Raynaud, C., Mohan, V.P., Laneelle, M.A., Yu, K., et al. (2000) Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol 36 : 630 637.
13. Gande, R., Gibson, K.J., Brown, A.K., Krumbach, K., Dover, L.G., Sahm, H., et al. (2004) Acyl-CoA carboxylases (accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycolic acid biosynthesis in Corynebacterianeae such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J Biol Chem 279 : 44847 44857.
14. Gao, L.Y., Laval, F., Lawson, E.H., Groger, R.K., Woodruff, A., Morisaki, J.H., et al. (2003) Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol Microbiol 49 : 1547 1563.
15. Glickman, M.S., Cox, J.S. Jacobs, W.R., Jr. (2000) A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol Cell 5 : 717 727.
16. Glickman, M.S. Jacobs, W.R., Jr. (2001) Microbial pathogenesis of Mycobacterium tuberculosis: dawn of a discipline. Cell 104 : 477 485.
17. Gokhale, R.S., Saxena, P., Chopra, T. Mohanty, D. (2007) Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. Nat Prod Rep 24 : 267 277.
18. Greenstein, A.E., Grundner, C., Echols, N., Gay, L.M., Lombana, T.N., Miecskowski, C.A., et al. (2005) Structure/function studies of Ser/Thr and Tyr protein phosphorylation in Mycobacterium tuberculosis. J Mol Microbiol Biotechnol 9 : 167 181.
19. Hayashi, T., Yamamoto, O., Sasaki, H., Okazaki, H. Kawaguchi, A. (1984) Inhibition of fatty acid synthesis by the antibiotic thiolactomycin. J Antibiot (Tokyo) 37 : 1456 1461.
20. Heath, R.J. Rock, C.O. (2002) The Claisen condensation in biology. Nat Prod Rep 19 : 581 596.
21. Heath, R.J. Rock, C.O. (2004) Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Invest Drugs 5 : 146 153.
22. Hunter, R.L., Olsen, M., Jagannath, C. Actor, J.K. (2006a) Trehalose 6,6′-dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice. Am J Pathol 168 : 1249 1261.
23. Hunter, R.L., Venkataprasad, N. Olsen, M.R. (2006b) The role of trehalose dimycolate (cord factor) on morphology of virulent M. tuberculosis in vitro. Tuberculosis (Edinb) 86 : 349 356.
24. Jones, P.B., Parrish, N.M., Houston, T.A., Stapon, A., Bansal, N.P., Dick, J.D. Townsend, C.A. (2000) A new class of antituberculosis agents. J Med Chem 43 : 3304 3314.
25. Kamal, A., Shaik, A.A., Sinha, R., Yadav, J.S. Arora, S.K. (2005) Antitubercular agents. Part 2: New thiolactomycin analogues active against Mycobacterium tuberculosis. Bioorg Med Chem Lett 15 : 1927 1929.
26. Kim, P., Zhang, Y.M., Shenoy, G., Nguyen, Q.A., Boshoff, H.I., Manjunatha, U.H., et al. (2006) Structure-activity relationships at the 5-position of thiolactomycin: an intact (5R)-isoprene unit is required for activity against the condensing enzymes from Mycobacterium tuberculosis and Escherichia coli. J Med Chem 49 : 159 171.
27. Kremer, L., Baulard, A.R. Besra, G.S. (2000a) Genetics of mycolic acid biosynthesis. In Molecular Genetics of Mycobacteria. Hatfull, G.F. Jacobs, W.R., Jr. (eds). Washington, DC : American Society for Microbiology Press, pp. 173 190.
28. Kremer, L., Douglas, J.D., Baulard, A.R., Morehouse, C., Guy, M.R., Alland, D., et al. (2000b) Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis. J Biol Chem 275 : 16857 16864.
29. Kremer, L., Nampoothiri, K.M., Lesjean, S., Dover, L.G., Graham, S., Betts, J., et al. (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 : 27967 27974.
30. Kremer, L., Dover, L.G., Carrere, S., Nampoothiri, K.M., Lesjean, S., Brown, A.K., et al. (2002) Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis. Biochem J 364 : 423 430.
31. Kremer, L., Dover, L.G., Morbidoni, H.R., Vilcheze, C., Maughan, W.N., Baulard, A., et al. (2003) Inhibition of InhA activity, but not KasA activity, induces formation of a KasA-containing complex in mycobacteria. J Biol Chem 278 : 20547 20554.
32. Lamichhane, G., Zignol, M., Blades, N.J., Geiman, D.E., Dougherty, A., Grosset, J., et al. (2003) A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Proc Natl Acad Sci USA 100 : 7213 7218.
33. Larsen, M.H., Vilcheze, C., Kremer, L., Besra, G.S., Parsons, L., Salfinger, M., et al. (2002) Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis. Mol Microbiol 46 : 453 466.
34. Lea-Smith, D.J., Pyke, J.S., Tull, D., McConville, M.J., Coppel, R.L. Crellin, P.K. (2007) The reductase that catalyzes mycolic motif synthesis is required for efficient attachment of mycolic acids to arabinogalactan. J Biol Chem 282 : 11000 11008.
35. Marrakchi, H., Ducasse, S., Labesse, G., Montrozier, H., Margeat, E., Emorine, L., et al. (2002) MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology 148 : 951 960.
36. Mdluli, K., Slayden, R.A., Zhu, Y., Ramaswamy, S., Pan, X., Mead, D., Crane, D.D., Musser, J.M. Barry, C.E., 3rd (1998) Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid. Science 280 : 1607 1610.
37. Molle, V., Brown, A.K., Besra, G.S., Cozzone, A.J. Kremer, L. (2006) The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation. J Biol Chem 281 : 30094 30103.
38. Ojha, A., Anand, M., Bhatt, A., Kremer, L., Jacobs, W.R., Jr. Hatfull, G.F. (2005) GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria. Cell 123 : 861 873.
39. Papavinasasundaram, K.G., Chan, B., Chung, J.H., Colston, M.J., Davis, E.O. Av-Gay, Y. (2005) Deletion of the Mycobacterium tuberculosis pknH gene confers a higher bacillary load during the chronic phase of infection in BALB/c mice. J Bacteriol 187 : 5751 5760.
40. Parrish, N.M., Houston, T., Jones, P.B., Townsend, C. Dick, J.D. (2001) In vitro activity of a novel antimycobacterial compound, N- octanesulfonylacetamide, and its effects on lipid and mycolic acid synthesis. Antimicrob Agents Chemother 45 : 1143 1150.
41. Portevin, D., De Sousa-D'Auria, C., Houssin, C., Grimaldi, C., Chami, M., Daffe, M. Guilhot, C. (2004) A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms. Proc Natl Acad Sci USA 101 : 314 319.
42. Price, A.C., Choi, K.H., Heath, R.J., Li, Z., White, S.W. Rock, C.O. (2001) Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J Biol Chem 276 : 6551 6559.
43. Quemard, A., Sacchettini, J.C., Dessen, A., Vilcheze, C., Bittman, R., Jacobs, W.R., Jr. Blanchard, J.S. (1995) Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis. Biochemistry 34 : 8235 8241.
44. Rao, V., Fujiwara, N., Porcelli, S.A. Glickman, M.S. (2005) Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule. J Exp Med 201 : 535 543.
45. Rao, V., Gao, F., Chen, B., Jacobs, W.R., Jr. Glickman, M.S. (2006) Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence. J Clin Invest 116 : 1660 1667.
46. Sassetti, C.M., Boyd, D.H. Rubin, E.J. (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48 : 77 84.
47. Scarsdale, J.N., Kazanina, G., He, X., Reynolds, K.A. Wright, H.T. (2001) Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III. J Biol Chem 276 : 20516 20522.
48. Schaeffer, M.L., Agnihotri, G., Volker, C., Kallender, H., Brennan, P.J. Lonsdale, J.T. (2001) Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB. J Biol Chem 276 : 47029 47037.
49. Senior, S.J., Illarionov, P.A., Gurcha, S.S., Campbell, I.B., Schaeffer, M.L., Minnikin, D.E. Besra, G.S. (2003) Biphenyl-based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme. Bioorg Med Chem Lett 13 : 3685 3688.
50. Senior, S.J., Illarionov, P.A., Gurcha, S.S., Campbell, I.B., Schaeffer, M.L., Minnikin, D.E. Besra, G.S. (2004) Acetylene-based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme. Bioorg Med Chem Lett 14 : 373 376.
51. Shawver, L.K., Slamon, D. Ullrich, A. (2002) Smart drugs: tyrosine kinase inhibitors in cancer therapy. Cancer Cell 1 : 117 123.
52. Slayden, R.A., Lee, R.E., Armour, J.W., Cooper, A.M., Orme, I.M., Brennan, P.J. Besra, G.S. (1996) Antimycobacterial action of thiolactomycin: an inhibitor of fatty acid and mycolic acid synthesis. Antimicrob Agents Chemother 40 : 2813 2819.
53. Slayden, R.A. Barry, C.E., 3rd (2002) The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis (Edinb) 82 : 149 160.
54. Smith, S., Witkowski, A. Joshi, A.K. (2003) Structural and functional organization of the animal fatty acid synthase. Prog Lipid Res 42 : 289 317.
55. Sridharan, S., Wang, L., Brown, A.K., Dover, L.G., Kremer, L., Besra, G.S. Sacchettini, J.C. (2007) X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB). J Mol Biol 366 : 469 480.
56. Starck, J., Kallenius, G., Marklund, B.I., Andersson, D.I. Akerlund, T. (2004) Comparative proteome analysis of Mycobacterium tuberculosis grown under aerobic and anaerobic conditions. Microbiology 150 : 3821 3829.
57. Takayama, K. Qureshi, N. (1984) Structure and synthesis of lipids. In The Mycobacteria: a Sourcebook. Kubica, G.P. Wayne, L.G. (eds). New York, NY : Marcel Dekker, pp. 315 344.
58. Takayama, K., Wang, C. Besra, G.S. (2005) Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18 : 81 101.
59. Trivedi, O.A., Arora, P., Sridharan, V., Tickoo, R., Mohanty, D. Gokhale, R.S. (2004) Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature 428 : 441 445.
60. Veyron-Churlet, R., Guerrini, O., Mourey, L., Daffe, M. Zerbib, D. (2004) Protein-protein interactions within the Fatty Acid Synthase-II system of Mycobacterium tuberculosis are essential for mycobacterial viability. Mol Microbiol 54 : 1161 1172.
61. Vilcheze, C., Wang, F., Arai, M., Hazbon, M.H., Colangeli, R., Kremer, L., et al. (2006) Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nat Med 12 : 1027 1029.
62. Walburger, A., Koul, A., Ferrari, G., Nguyen, L., Prescianotto-Baschong, C., Huygen, K., et al. (2004) Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 304 : 1800 1804.
63. Yuan, Y., Zhu, Y., Crane, D.D. Barry, C.E., 3rd (1998) The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Mol Microbiol 29 : 1449 1458.
64. Zhang, Y., Wade, M.M., Scorpio, A., Zhang, H. Sun, Z. (2003) Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J Antimicrob Chemother 52 : 790 795.
65. Zimhony, O., Cox, J.S., Welch, J.T., Vilcheze, C. Jacobs, W.R., Jr. (2000) Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med 6 : 1043 1047.
66. Zimhony, O., Vilcheze, C., Arai, M., Welch, J.T. Jacobs, W.R., Jr. (2007) Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother 51 : 752 754.