Fatty acid biosynthesis as a target for novel antibacterials

Current Opinion in Investigational Drugs

Volumn 5, Issue 2, 2004, Pages 146-153

  Heath, Richard J ^a   Rock, Charles O ^a,b  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

Author keywords

Antibacterial; Cerulenin; Condensing enzymes; Enoyl ACP reductase; FabB; FabF; FabG; FabH; FabI; Isoniazid; Ketoacyl ACP reductase; Thiolactomycin; Triclosan

Indexed keywords

ANTIINFECTIVE AGENT; ENZYME INHIBITOR; FATTY ACID;

ANIMAL; BIOSYNTHESIS; DRUG ANTAGONISM; DRUG DELIVERY SYSTEM; HUMAN; METHODOLOGY; REVIEW;

ANIMALS; ANTI-BACTERIAL AGENTS; DRUG DELIVERY SYSTEMS; ENZYME INHIBITORS; FATTY ACIDS; HUMANS;

EID: 3042764816     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (74)

1. Rock CO, Cronan JE Jr: Escherichia coli as a model for the regulation of dissociable (type II) fatty acid biosynthesis. Biochim Biophys Acta (1996) 1302(1):1-16.
2. Heath RJ, Jackowski S, Rock CO: Fatty acid and phospholipid metabolism in prokaryotes. In: Biochemistry of Lipids, Lipoproteins and Membranes. 4th Edition, Vance JE, Vance DE (Eds), Elsevier, New York, NY, USA (2002) 36:55-92.
3. Smith S: The animal fatty acid synthase: One gene, one polypeptide, seven enzymes. FASEB J (1994) 8(15):1248-1259.
4. Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res (2001) 40(6):467-497.
5. Egan AF, Russell RRB: Conditional mutations affecting the cell envelope of Escherichia coli K-12. Genet Res (1973) 21(2):139-152.
6. Zhang Y, Cronan JE Jr: Transcriptional analysis of essential genes of the Escherichia coli fatty acid biosynthesis gene cluster by functional replacement with the analogous Salmonella typhimurium gene cluster. J Bacteriol (1998) 180(13):3295-3303.
7. Heath RJ, Rock CO: The Claisen condensation in biology. Nat Prod Rep (2002) 19(5):581-596.
8. Banerjee A, Dubnau E, Quémard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs WR Jr: inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science (1994) 263(5144):227-230.
9. Dessen A, Quémard A, Blanchard JS, Jacobs WR Jr, Sacchettini JC: Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science (1995) 267(5204): 1638-1641.
10. Marrakchi H, Laneelle G, Quemard A: InhA, a target of the antituberculous drug isoniazid, is involved in a mycobacterial fatty acid elongation system, FAS-II. Microbiology (2000) 146(2):289-296.
11. Baldock C, de Boer G-J, Rafferty JB, Stuitje AR, Rice DW: Mechanism of action of diazaborines. Biochem Pharmacol(1998) 55(10):1541- 1550.
12. Davis MC, Franzblau SG, Martin AR: Syntheses and evaluation of benzodiazaborine compounds against M tuberculosis H37Rv in vitro. Bioorg Med Chem Lett (1998) 8(7):843-846.
13. Turnowsky F, Fuchs K, Jeschek C, Högenauer G: envM genes of Salmonella typhimurium and Escherichia coli. J Bacteriol (1989) 171(12):6555-6565.
14. Lam C, Turnowsky C, Hogenauer G, Schutze E: Effect of a diazaborine derivative (Sa 84.474) on the virulence of Escherichia coli. J Antimicrob Chemother (1987) 20(1):37-45.
15. Grassberger MA, Turnowsky F, Hildebrandt J: Preparation and antibacterial activities of new 1,2,3-diazaborine derivatives and analogues. J Med Chem (1984) 27(8):947-953.
16. Heath RJ, Rock CO: Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J Biol Chem (1995) 270(44):26538-26542.
17. Hoang TT, Schweizer HP: Characterization of Pseudomonas aeruginosa enoyl-acyl carrier protein reductase (FabI): A target for the antimicrobial triclosan and its role in acylated homoserine lactone synthesis. J Bacteriol (1999) 181(17):5489-5497.
18. Heath RJ, Su N, Murphy CK, Rock CO: The enoyl-[acyl-carrier-protein] reductases, FabI and FabL, from Bacillus subtilis. J Biol Chem (2000) 275(51):40128-40133.
19. Heath RJ, Rock CO: A triclosan-resistant bacterial enzyme. Nature (2000) 406(6792):145-146.
20. Bhargava HN, Leonard PA: Triclosan: Applications and safety. Am J Infect Control (1996) 24(3):209-218.
21. Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO: Mechanism of triclosan inhibition of bacterial fatty acid synthesis. J Biol Chem (1999) 274(16):11110-11114.
22. Heath RJ, Li J, Roland GE, Rock CO: Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene. J Biol Chem (2000) 275(7):4654-4659.
23. McMurry LM, Oethinger M, Levy SB: Triclosan targets lipid synthesis. Nature (1998) 394(6693):531-532.
24. Heath RJ, Yu Y-T, Shapiro MA, Olson E, Rock CO: Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis. J Biol Chem (1998) 273(46):30316-30320.
25. Ward WH, Holdgate GA, Rowsell S, McLean EG, Pauptit RA, Clayton E, Nichols WW, Colls JG, Minshull CA, Jude DA, Mistry A et al: Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan. Biochemistry (1999) 38(38):12514- 12525.
26. Fan F, Yan K, Wallis NG, Reed S, Moore TD, Rittenhouse SF, DeWolf WE Jr, Huang J, McDevitt D, Miller WH, Seefeld MA et al: Defining and combating the mechanisms of triclosan resistance in clinical isolates of Staphylococcus aureus. Antimicrob Agents Chemother (2002) 46(11):3343-3347.
27. McMurry LM, McDermott PF, Levy SB: Genetic evidence that InhA of Mycobacterium smegmatis is a target for triclosan. Antimicrob Agents Chemother (1999) 43(3):711-713.
28. Parikh SL, Xiao G, Tonge PJ: Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis by triclosan and isoniazid. Biochemistry (2000) 39(26):7645-7650.
29. Mdluli K, Slayden RA, Zhu Y, Ramaswamy S, Pan X, Mead D, Crane DD, Musser JM, Barry CE 3rd: Inhibition of Mycobacterium tuberculosis β-ketoacyl ACP synthase by isoniazid. Science (1998) 280(5369):1607-1610.
30. Vilcheze C, Morbidoni HR, Weisbrod TR, Iwamoto H, Kuo M, Sacchettini JC, Jacobs WR Jr: 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 (2000) 182(14):4059-4067.
31. Larsen MH, Vilcheze C, Kremer L, Besra GS, Parsons L, Salfinger M, Heifets L, Hazbon MN, Alland D, Sacchettini JC, Jacobs WR Jr: Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M bovis BCG and M tuberculosis. Mol Microbiol (2002) 46(2):453-466.
32. Baldock C, Rafferty JB, Sedelnikova SE, Baker PJ, Stuitje AR, Slabas AR, Hawkes TR, Rice DW: A mechanism of drug action revealed by structural studies of enoyl reductase. Science (1996) 274(5295):2107-2110.
33. + at 2.1 Å resolution. J Mol Biol (1998) 284(5):1529-1546.
34. Rozwarski DA, Grant GA, Barton DH, Jacobs WR, Sacchettini JC: Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science (1998) 279(5347):98- 102.
35. Heerding DA, Chan G, DeWolf WE, Fosberry AP, Janson CA, Jaworski DD, McManus E, Miller WH, Moore TD, Payne DJ, Qiu X et al: 1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI). Bioorg Med Chem Lett (2001) 11(16):2061-2065.
36. Payne DJ, Miller WH, Berry V, Brosky J, Burgess WJ, Chen E, DeWolf EW Jr, Fosberry AP, Greenwood R, Head MS, Heerding DA et al: Discovery of a novel and potent class of FabI-directed antibacterial agents. Antimicrob Agents Chemother (2002) 46(10):3118-3124.
37. Miller WH, Seefeld MA, Newlander KA, Uzinskas IN, Burgess WJ, Heerding DA, Yuan CC, Head MS, Payne DJ, Rittenhouse SF, Moore TD et al: Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI). J Med Chem (2002) 45(15):3246-3256.
38. Li Q, Lee JY, Castillo R, Hixon MS, Pujol C, Doppalapudi VR, Shepard HM, Wahl GM, Lobl TJ, Chan MF: NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against β-lactamase-producing strains. Antimicrob Agents Chemother (2002) 46(5):1262-1268.
39. Tan L, Nielsen NH, Young DC, Trizna Z: Use of antimicrobial agents in consumer products. Arch Dermatol (2002) 138(8):1082-1086.
40. D'Agnolo G, Rosenfeld IS, Awaya J, Omura S, Vagelos PR: Inhibition of fatty acid biosynthesis by the antibiotic cerulenin. Specific inactivation of β-ketoacyl-acyl carrier protein synthetase. Biochim Biophys Acta (1973) 326(2):155-166.
41. Moche M, Schneider G, Edwards P, Dehesh K, Lindqvist Y: Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl-acyl carrier protein synthase. J Biol Chem (1999) 274(10):6031-6034.
42. Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO: Inhibition of β-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J Biol Chem (2001) 276(9):6551-6559.
43. Nomura S, Horiuchi T, Omura S, Hata T: The action mechanism of cerulenin. I. Effect of cerulenin on sterol and fatty acid biosynthesis in yeast. J Biochem (1972) 71(5):783-796.
44. Kuhajda FP, Pizer ES, Li JN, Mani NS, Frehywot GL, Townsend CA: Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci USA (2000) 97(7):3450-3454.
45. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP: Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science (2000) 288(5475):2379-2381.
46. Oishi H, Noto T, Sasaki H, Suzuki K, Hayashi T, Okazaki H, Ando K, Sawada M: Thiolactomycin, a new antibiotic. I. Taxonomy of the producing organism, fermentation and biological properties. J Antibiot (1982) 35(4):391-395.
47. Hayashi T, Yamamoto O, Sasaki H, Kawaguchi A, Okazaki H: Mechanism of action of the antibiotic thiolactomycin inhibition of fatty acid synthesis of Escherichia coli. Biochem Biophys Res Commun (1983) 115(3):1108-1113.
48. Noto T, Miyakawa S, Oishi H, Endo H, Okazaki H: Thiolactomycin, a new antibiotic. III. In vitro antibacterial activity. J Antibiot (1982) 35(4):401-410.
49. Kremer L, Douglas JD, Baulard AR, Morehouse C, Guy MR, Alland D, Dover LG, Lakey JH, Jacobs WR Jr, Brennan PJ, Minnikin DE et al: Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis. J Biol Chem (2000) 275(22):16857-16864.
50. Waller RF, Keeling PJ, Donald RG, Striepen B, Handman E, Lang-Unnasch N, Cowman AF, Besra GS, Roos DS, McFadden GI: Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proc Natl Acad Sci USA (1998) 95(21):12352-12357.
51. Miyakawa S, Suzuki K, Noto T, Harada Y, Okazaki H: Thiolactomycin, a new antibiotic. IV. Biological properties and chemotherapeutic activity in mice. J Antibiot (1982) 35(4):411-419.
52. Huang W, Jia J, Edwards P, Dehesh K, Schneider G, Lindqvist Y: Crystal structure of β-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes. EMBO J (1998) 17(5):1183-1191.
53. Davies C, Heath RJ, White SW, Rock CO: The 1.8 Å cystal structure and active-site architecture of β-ketoacyl-acyl carrier protein synthase III (FabH) from Escherichia coli. Structure Fold Design (2000) 8(2):185-195.
54. Tsay JT, Oh W, Larson TJ, Jackowski S, Rock CO: Isolation and characterization of the β-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J Biol Chem (1992) 267(10):6807-6814.
55. Tsay JT, Rock CO, Jackowski S: Overproduction of β-ketoacyl-acyl carrier protein synthase I imparts thiolactomycin resistance to Escherichia coli K-12. J Bacteriol (1992) 174(2):508-513.
56. Jackowski S, Rock CO: Acetoacetyl-acyl carrier protein synthase, a potential regulator of fatty acid biosynthesis in bacteria. J Biol Chem (1987) 262(16):7927-7931.
57. Schujman GE, Choi K-H, Altabe S, Rock CO, de Mendoza D: Response of Bacillus subtilis to cerulenin and acquisition of resistance. J Bacteriol (2001) 183(10):3032-3040.
58. Furukawa H, Tsay J-T, Jackowski S, Takamura Y, Rock CO: Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB. J Bacteriol (1993) 175(12):3723-3729.
59. Jackowski S, Zhang Y-M, Price AC, White SW, Rock CO: A missense mutation in the fabB (β-ketoacyl-acyl carrier protein synthase I) gene confers thiolactomycin resistance to Escherichia coli. Antimicrob Agents Chem (2002) 46(5):1246-1252.
60. Jones AL, Herbert D, Rutter AJ, Dancer JE, Harwood JL: Novel inhibitors of the condensing enzymes of the type II fatty acid synthase of pea (Pisum sativum). Biochem J (2000) 347(1):205-209.
61. Douglas JD, Senior SJ, Morehouse C, Phetsukiri B, Campbell IB, Besra GS, Minnikin DE: Analogues of thiolactomycin: Potential drugs with enhanced anti-mycobacterial activity. Microbiology (2002) 148(10):3101- 3109.
62. Sakya SM, Suarez-Contreras M, Dirlam JP, O'Connell TN, Hayashi SF, Santoro SL, Kamicker BJ, George DM, Ziegler CB: Synthesis and structure-activity relationships of thiotetronic acid analogues of thiolactomycin. Bioorg Med Chem Lett (2001) 11(20):2751-2754.
63. He X, Reynolds KA: Purification, characterization, and identification of novel inhibitors of the β-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus. Antimicrob Agents Chemother (2002) 46(5):1310-1318.
64. Baum EZ, Montenegro DA, Licata L, Turchi I, Webb GC, Foleno BD, Bush K: Identification and characterization of new inhibitors of the Escherichia coli MurA enzyme. Antimicrob Agents Chemother (2001) 45(11):3182-3188.
65. Price AC, Zhang Y-M, Rock CO, White SW: The structure of β-ketoacyl-[acyl carrier protein] reductase from Escherichia coli: Negative cooperativity and its structural basis. Biochemistry (2001) 40(43):12772-12781.
66. Helmkamp GM Jr, Brock DJH, Bloch K: β-Hydroxydecanoyl thioester dehydrase. Specificity of substrates and acetylenic inhibitors. J Biol Chem (1968) 243(12):3229-3231.
67. Leesong M, Henderson BS, Gillig JR, Schwab JM, Smith JL: Structure of a dehydratase-isomerase from the bacterial pathway for biosynthesis of unsaturated fatty acids: Two catalytic activities in one active site. Structure (1996) 4(3):253-264.
68. Davis MS, Solbiati J, Cronan JE Jr: Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli. J Biol Chem (2000) 275(37):28593-28598.
69. Amspacher DR, Blanchard CZ, Fronczek FR, Saraiva MC, Waldrop GL, Strongin RM: Synthesis of a reaction intermediate analogue of biotin-dependent carboxylases via a selective derivatization of biotin. Org Lett (1999) 1(1):99-102.
70. Blanchard CZ, Amspacher D, Strongin R, Waldrop GL: Inhibition of biotin carboxylase by a reaction intermediate analog: Implications for the kinetic mechanism. Biochem Biophys Res Commun (1999) 266(2):466-471.
71. Waldrop GL, Rayment I, Holden HM: Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase. Biochemistry (1994) 33(34):10249-10256.
72. Thoden JB, Blanchard CZ, Holden HM, Waldrop GL: Movement of the biotin carboxylase B-domain as a result of ATP binding. J Biol Chem (2000) 275(21):16183-16190.
73. Nikolskaya T, Zagnitko O, Tevzadze G, Haselkorn R, Gornicki P: Herbicide sensitivity determinant of wheat plastid acetyl-CoA carboxylase is located in a 400-amino acid fragment of the carboxyltransferase domain. Proc Natl Acad Sci USA (1999) 96(25):14647-14651.
74. Zhang YM, Rao MS, Heath RJ, Price AC, Olson AJ, Rock CO, White SW: Identification and analysis of the acyl carrier protein (ACP) docking site on β-ketoacyl-ACP synthase III. J Biol Chem (2001) 276(11):8231-8238.