Characterization of the Mycobacterial Acyl-CoA Carboxylase Holo Complexes Reveals Their Functional Expansion into Amino Acid Catabolism
Tuberculosis is deadly human disease caused by infection with the bacterium Mycobacterium tuberculosis. This pathogen has a complex metabolism with many genes required for the synthesis of components of its unique cell envelope. We have investigated a family of closely related genes coding for different acyl CoA carboxylase enzyme complexes with previously unexplained genetic redundancy that have been thought to have an involvement in the synthesis of these cell envelope components. We identified five functional multienzyme complexes. Of the two complexes with hitherto unknown function we chose to investigate, one specifically and to our surprise it is required for the degradation of the amino acid leucine. To our knowledge this is the first demonstration that mycobacteria have a specific pathway for leucine degradation and thus broaden the functional diversity associated with acyl CoA carboxylase coding genes.
Vyšlo v časopise:
Characterization of the Mycobacterial Acyl-CoA Carboxylase Holo Complexes Reveals Their Functional Expansion into Amino Acid Catabolism. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004623
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004623
Souhrn
Tuberculosis is deadly human disease caused by infection with the bacterium Mycobacterium tuberculosis. This pathogen has a complex metabolism with many genes required for the synthesis of components of its unique cell envelope. We have investigated a family of closely related genes coding for different acyl CoA carboxylase enzyme complexes with previously unexplained genetic redundancy that have been thought to have an involvement in the synthesis of these cell envelope components. We identified five functional multienzyme complexes. Of the two complexes with hitherto unknown function we chose to investigate, one specifically and to our surprise it is required for the degradation of the amino acid leucine. To our knowledge this is the first demonstration that mycobacteria have a specific pathway for leucine degradation and thus broaden the functional diversity associated with acyl CoA carboxylase coding genes.
Zdroje
1. Cronan JE Jr., Waldrop GL (2002) Multi-subunit acetyl-CoA carboxylases. Prog Lipid Res 41: 407–435. 12121720
2. Tong L (2013) Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci 70: 863–891. doi: 10.1007/s00018-012-1096-0 22869039
3. Tong L, Harwood HJ Jr., (2006) Acetyl-coenzyme A carboxylases: versatile targets for drug discovery. J Cell Biochem 99: 1476–1488. 16983687
4. Miller JR, Dunham S, Mochalkin I, Banotai C, Bowman M, et al. (2009) A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore. Proc Natl Acad Sci U S A 106: 1737–1742. doi: 10.1073/pnas.0811275106 19164768
5. Gago G, Diacovich L, Arabolaza A, Tsai SC, Gramajo H (2011) Fatty acid biosynthesis in actinomycetes. FEMS Microbiol Rev 35: 475–497. doi: 10.1111/j.1574-6976.2010.00259.x 21204864
6. Gago G, Kurth D, Diacovich L, Tsai SC, Gramajo H (2006) Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J Bacteriol 188: 477–486. 16385038
7. Daniel J, Oh TJ, Lee CM, Kolattukudy PE (2007) AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis. J Bacteriol 189: 911–917. 17114269
8. Kurth DG, Gago GM, de la Iglesia A, Bazet Lyonnet B, Lin TW, et al. (2009) ACCase 6 is the essential acetyl-CoA carboxylase involved in fatty acid and mycolic acid biosynthesis in mycobacteria. Microbiology 155: 2664–2675. doi: 10.1099/mic.0.027714-0 19423629
9. Karakousis PC, Bishai WR, Dorman SE (2004) Mycobacterium tuberculosis cell envelope lipids and the host immune response. Cell Microbiol 6: 105–116. 14706097
10. Camacho LR, Constant P, Raynaud C, Laneelle MA, Triccas JA, et al. (2001) Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J Biol Chem 276: 19845–19854. 11279114
11. Savvi S, Warner DF, Kana BD, McKinney JD, Mizrahi V, et al. (2008) Functional characterization of a vitamin B12-dependent methylmalonyl pathway in Mycobacterium tuberculosis: implications for propionate metabolism during growth on fatty acids. J Bacteriol 190: 3886–3895. doi: 10.1128/JB.01767-07 18375549
12. Portevin D, de Sousa-D’Auria C, Montrozier H, Houssin C, Stella A, et al. (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: 8862–8874. 15632194
13. Oh TJ, Daniel J, Kim HJ, Sirakova TD, Kolattukudy PE (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: 3899–3908. 16354663
14. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537–544. 9634230
15. Haase FC, Henrikson KP, Treble DH, Allen SH (1982) The subunit structure and function of the propionyl coenzyme A carboxylase of Mycobacterium smegmatis. J Biol Chem 257: 11994–11999. 7118926
16. Diacovich L, Peiru S, Kurth D, Rodriguez E, Podesta F, et al. (2002) Kinetic and structural analysis of a new group of Acyl-CoA carboxylases found in Streptomyces coelicolor A3(2). J Biol Chem 277: 31228–31236. 12048195
17. Huang CS, Ge P, Zhou ZH, Tong L (2011) An unanticipated architecture of the 750-kDa alpha6beta6 holoenzyme of 3-methylcrotonyl-CoA carboxylase. Nature 481: 219–223. doi: 10.1038/nature10691 22158123
18. Gande R, Gibson KJ, Brown AK, Krumbach K, Dover LG, 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. 15308633
19. Zimmermann M, Thormann V, Sauer U, Zamboni N (2013) Nontargeted profiling of coenzyme A thioesters in biological samples by tandem mass spectrometry. Anal Chem 85: 8284–8290. doi: 10.1021/ac401555n 23895734
20. Massey LK, Sokatch JR, Conrad RS (1976) Branched-chain amino acid catabolism in bacteria. Bacteriol Rev 40: 42–54. 773366
21. Fendt SM, Buescher JM, Rudroff F, Picotti P, Zamboni N, et al. (2010) Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity. Mol Syst Biol 6: 356. doi: 10.1038/msb.2010.11 20393576
22. Hondalus MK, Bardarov S, Russell R, Chan J, Jacobs WR Jr., et al. (2000) Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect Immun 68: 2888–2898. 10768986
23. Venugopal A, Bryk R, Shi S, Rhee K, Rath P, et al. (2011) Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe 9: 21–31. doi: 10.1016/j.chom.2010.12.004 21238944
24. Balhana RJ, Swanston SN, Coade S, Withers M, Sikder MH, et al. (2013) bkaR is a TetR-type repressor that controls an operon associated with branched-chain keto-acid metabolism in Mycobacteria. FEMS Microbiol Lett 345: 132–140. doi: 10.1111/1574-6968.12196 23763300
25. Holton SJ, King-Scott S, Nasser Eddine A, Kaufmann SH, Wilmanns M (2006) Structural diversity in the six-fold redundant set of acyl-CoA carboxyltransferases in Mycobacterium tuberculosis. FEBS Lett 580: 6898–6902. 17157300
26. Zhang H, Yang Z, Shen Y, Tong L (2003) Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase. Science 299: 2064–2067. 12663926
27. Bilder P, Lightle S, Bainbridge G, Ohren J, Finzel B, et al. (2006) The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme. Biochemistry 45: 1712–1722. 16460018
28. Lin TW, Melgar MM, Kurth D, Swamidass SJ, Purdon J, et al. (2006) Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 103: 3072–3077. 16492739
29. Huang CS, Sadre-Bazzaz K, Shen Y, Deng B, Zhou ZH, et al. (2010) Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. Nature 466: 1001–1005. doi: 10.1038/nature09302 20725044
30. Reddy MC, Breda A, Bruning JB, Sherekar M, Valluru S, et al. (2014) Structure, activity, and inhibition of the Carboxyltransferase beta-subunit of acetyl coenzyme A carboxylase (AccD6) from Mycobacterium tuberculosis. Antimicrob Agents Chemother 58: 6122–6132. doi: 10.1128/AAC.02574-13 25092705
31. Tran TH, Hsiao YS, Jo J, Chou CY, Dietrich LE, et al. (2014) Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase. Nature. doi: 10.1038/nature14135 25533962
32. Williams KJ, Joyce G, Robertson BD (2010) Improved mycobacterial tetracycline inducible vectors. Plasmid 64: 69–73. doi: 10.1016/j.plasmid.2010.04.003 20434484
33. Li MZ, Elledge SJ (2007) Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC. Nat Methods 4: 251–256. 17293868
34. Plocinski P, Laubitz D, Cysewski D, Stodus K, Kowalska K, et al. (2014) Identification of protein partners in mycobacteria using a single-step affinity purification method. PLoS One 9: e91380. doi: 10.1371/journal.pone.0091380 24664103
35. van Kessel JC, Hatfull GF (2007) Recombineering in Mycobacterium tuberculosis. Nat Methods 4: 147–152. 17179933
36. Bardarov S, Bardarov Jr S Jr., Pavelka Jr MS Jr., Sambandamurthy V, Larsen M, et al. (2002) Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis. Microbiology 148: 3007–3017. 12368434
37. Piuri M, Hatfull GF (2006) A peptidoglycan hydrolase motif within the mycobacteriophage TM4 tape measure protein promotes efficient infection of stationary phase cells. Mol Microbiol 62: 1569–1585. 17083467
38. Poulsen C, Holton S, Geerlof A, Wilmanns M, Song YH (2010) Stoichiometric protein complex formation and over-expression using the prokaryotic native operon structure. FEBS Lett 584: 669–674. doi: 10.1016/j.febslet.2009.12.057 20085764
39. Noens EE, Williams C, Anandhakrishnan M, Poulsen C, Ehebauer MT, et al. (2011) Improved mycobacterial protein production using a Mycobacterium smegmatis groEL1DeltaC expression strain. BMC Biotechnol 11: 27. doi: 10.1186/1472-6750-11-27 21439037
40. Guchhait RB, Polakis SE, Dimroth P, Stoll E, Moss J, et al. (1974) Acetyl coenzyme A carboxylase system of Escherichia coli. Purification and properties of the biotin carboxylase, carboxyltransferase, and carboxyl carrier protein components. J Biol Chem 249: 6633–6645. 4154089
41. Tang G, Peng L, Baldwin PR, Mann DS, Jiang W, et al. (2007) EMAN2: an extensible image processing suite for electron microscopy. J Struct Biol 157: 38–46. 16859925
42. van Heel M, Harauz G, Orlova EV, Schmidt R, Schatz M (1996) A new generation of the IMAGIC image processing system. J Struct Biol 116: 17–24. 8742718
43. Shaikh TR, Gao H, Baxter WT, Asturias FJ, Boisset N, et al. (2008) SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs. Nat Protoc 3: 1941–1974. doi: 10.1038/nprot.2008.156 19180078
44. Eswar N, Eramian D, Webb B, Shen MY, Sali A (2008) Protein structure modeling with MODELLER. Methods Mol Biol 426: 145–159. doi: 10.1007/978-1-60327-058-8_8 18542861
45. Shen MY, Sali A (2006) Statistical potential for assessment and prediction of protein structures. Protein Sci 15: 2507–2524. 17075131
46. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213–221. doi: 10.1107/S0907444909052925 20124702
47. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372: 774–797. 17681537
48. Laval F, Laneelle MA, Deon C, Monsarrat B, Daffe M (2001) Accurate molecular mass determination of mycolic acids by MALDI-TOF mass spectrometry. Anal Chem 73: 4537–4544. 11575804
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 2
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Control of Murine Cytomegalovirus Infection by γδ T Cells
- ATPaseTb2, a Unique Membrane-bound FoF1-ATPase Component, Is Essential in Bloodstream and Dyskinetoplastic Trypanosomes
- Rational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Using Prokaryotic Mutagenesis and In Vivo Bioluminescent Imaging
- Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection