The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog

  • Vasiliki Garefalaki
  • Evanthia Kontomina
  • Charalambos Ioannidis
  • Olga Savvidou
  • Christina Vagena-Pantoula
  • Maria-Giusy Papavergi
  • Ioannis Olbasalis
  • Dionysios Patriarcheas
  • Konstantina C. Fylaktakidou
  • Tamás Felföldi
  • Károly Márialigeti
  • Giannoulis Fakis
  • Sotiria BoukouvalaEmail author
Original Paper


Actinobacteria in the Tsukamurella genus are aerobic, high-GC, Gram-positive mycolata, considered as opportunistic pathogens and isolated from various environmental sources, including sites contaminated with oil, urban or industrial waste and pesticides. Although studies look into xenobiotic biotransformation by Tsukamurella isolates, the relevant enzymes remain uncharacterized. We investigated the arylamine N-acetyltransferase (NAT) enzyme family, known for its role in the xenobiotic metabolism of prokaryotes and eukaryotes. Xenobiotic sensitivity of Tsukamurella paurometabola type strain DSM 20162T was assessed, followed by cloning, recombinant expression and functional characterization of its single NAT homolog (TSUPD)NAT1. The bacterium appeared quite robust against chloroanilines, but more sensitive to 4-anisidine and 2-aminophenol. However, metabolic activity was not evident towards those compounds, presumably due to mechanisms protecting cells from xenobiotic entry. Of the pharmaceutical arylhydrazines tested, hydralazine was toxic, but the bacterium was less sensitive to isoniazid, a drug targeting mycolic acid biosynthesis in mycobacteria. Although (TSUPD)NAT1 protein has an atypical Cys-His-Glu (instead of the expected Cys-His-Asp) catalytic triad, it is enzymatically active, suggesting that this deviation is likely due to evolutionary adaptation potentially serving a different function. The protein was indeed found to use malonyl-CoA, instead of the archetypal acetyl-CoA, as its preferred donor substrate. Malonyl-CoA is important for microbial biosynthesis of fatty acids (including mycolic acids) and polyketide chains, and the corresponding enzymatic systems have common evolutionary histories, also linked to xenobiotic metabolism. This study adds to accummulating evidence suggesting broad phylogenetic and functional divergence of microbial NAT enzymes that goes beyond xenobiotic metabolism and merits investigation.


Acylated dichloroaniline derivatives Malonyl-coenzyme A N-acetyltransferase NAT enzyme family N-malonyltransferase Tsukamurella paurometabola Xenobiotics 



This research was partly funded by a Joint Research & Technology 2009 Programme between Greece and Hungary (Grant No. HUN40), co-financed by Greece, Hungary and the European Union (European Regional Development Fund-ERDF) through Operational Program “Competitiveness and Entrepreneurship” in the context of project “Bilateral, Multilateral and Regional R&T Cooperation” implemented by the Greek General Secretariat for Research and Technology (GSRT) and the Hungarian National Office for Research and Technology (NKTH), and conducted by the two partners in 2012–2014. E.K. is recipient of a Ph.D. scholarship (2016–2019) and her research is co-financed by Greece and the European Union (European Social Fund-ESF) through Operational Program “Human Resources Development, Education and Lifelong Learning” in the context of project “Strengthening Human Resources Research Potential via Doctorate Research” (MIS-5000432), implemented by the State Scholarships Foundation (ΙΚΥ). None of the funding bodies had any involvement in the study design, in the collection, analysis or interpretation of data, in the writing of the report or the decision to submit the article for publication.

Author contributions

VG performed the bulk of experimental procedures and data analyses; EK contributed to xenobiotic sensitivity tests and TLC assays; CI contributed to enzyme kinetic assays; OS, CVP and MGP contributed to DSF assays; IO and DP contributed to computational work; KF synthesized and characterised chemical compounds; TF, KM, GF and SB generated the biological material used and provided expert scientific input; KM, GF and SB conceived of, designed and pursued funding for the study; SB supervised the project, analysed data and wrote the manuscript. The materials and datasets generated during the study are available from SB on reasonable request. All authors reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11274_2019_2755_MOESM1_ESM.pdf (10.2 mb)
Supplementary file1 (PDF 10425 kb)


  1. Abou Mehrez O, Dossier-Berne F, Legube B (2016) Oxidation of 2-aminophenol to 2-amino-3H-phenoxazin-3-one with monochloramine in aqueous environment: a new method for APO synthesis? Chemosphere 145:464–469PubMedGoogle Scholar
  2. Abuhammad A, Lowe ED, McDonough MA, Shaw Stewart PD, Kolek SA, Sim E, Garman EF (2013) Structure of arylamine N-acetyltransferase from Mycobacterium tuberculosis determined by cross-seeding with the homologous protein from M. marinum: triumph over adversity. Acta Crystallogr D 69:1433–1446PubMedGoogle Scholar
  3. Anderton MC, Bhakta S, Besra GS, Jeavons P, Eltis LD, Sim E (2006) Characterization of the putative operon containing arylamine N-acetyltransferase (nat) in Mycobacterium bovis BCG. Mol Microbiol 59:181–192PubMedGoogle Scholar
  4. Andrews JM (2001) Determination of minimum inhibitory concentrations. J Antimicrob Chemother 48(Suppl 1):5–16PubMedGoogle Scholar
  5. Arnold M, Reittu A, von Wright A, Martikainen PJ, Suihko ML (1997) Bacterial degradation of styrene in waste gases using a peat filter. Appl Microbiol Biotechnol 48:738–744PubMedGoogle Scholar
  6. Arora PK (2015) Bacterial degradation of monocyclic aromatic amines. Front Microbiol 6:820PubMedPubMedCentralGoogle Scholar
  7. Bhakta S, Besra GS, Upton AM, Parish T, Sholto-Douglas-Vernon C, Gibson KJC, Knutton S, Gordon S, DaSilva RP, Anderton MC, Sim E (2004) Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target. J Exp Med 199:1191–1199PubMedPubMedCentralGoogle Scholar
  8. Boukouvala S (2018) Arylamine N-Acetyltransferase nomenclature. In: Sim E, Laurieri N (eds), Arylamine N-acetyltransferases in health and disease. Singapore, World Scientific Publishing Co Pte Ltd. CrossRefGoogle Scholar
  9. Boukouvala S, Fakis G (2005) Arylamine N-acetyltransferases: what we learn from genes and genomes. Drug Metab Rev 37:511–564PubMedGoogle Scholar
  10. Brooke EW, Davies SG, Mulvaney AW, Okada M, Pompeo F, Sim E, Vickers RJ, Westwood IM (2003) Synthesis and in vitro evaluation of novel small molecule inhibitors of bacterial arylamine N-acetyltransferases (NATs). Bioorg Med Chem Lett 13:2527–2530PubMedGoogle Scholar
  11. Cao H, Ma Q, Chen X, Xu Y (2017) DOOR: a prokaryotic operon database for genome analyses and functional inference. Brief Bioinform. CrossRefPubMedGoogle Scholar
  12. Chen X, Wang L, Du Y, Wu Y, Jia X, Yang Y, Hong B (2011) Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents. Molecules 16:9178–9193PubMedPubMedCentralGoogle Scholar
  13. Chiciudean I, Nie Y, Tanase A-M, Stoica I, Wu X-L (2018) Complete genome sequence of Tsukamurella sp. MH1: a wide-chain length alkane-degrading actinomycete. J Biotechnol 268:1–5PubMedGoogle Scholar
  14. Cocaign A, Kubiak X, Xu X, Garnier G, Li de la Sierra-Gallay I, Chi-Bui L, Dairou J, Busi F, Abuhammad A, Haouz A, Dupret JM, Herrmann JL, Rodrigues-Lima F (2014) Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus: differences from other mycobacterial isoforms and implications for selective inhibition. Acta Crystallogr D 70:3066–3079PubMedGoogle Scholar
  15. Collins MD, Smida J, Dorsch M, Stackebrandt E (1988) Tsukamurella gen. nov. Harboring Corynebacterium paurometabolum and Rhodococcus aurantiacus. Int J Syst Bacteriol 38(4):385–391Google Scholar
  16. Cresnar B, Petric S (2011) Cytochrome P450 enzymes in the fungal kingdom. Biochim Biophys Acta 1814:29–35PubMedGoogle Scholar
  17. Cronan JE, Thomas J (2009) Bacterial fatty acid synthesis and its relationships with polyketide synthetic pathways. Methods Enzymol 459:395–433PubMedPubMedCentralGoogle Scholar
  18. Delomenie C, Fouix S, Longuemaux S, Brahimi N, Bizet C, Picard B, Denamur E, Dupret JM (2001) Identification and functional characterization of arylamine N-acetyltransferases in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic acid. J Bacteriol 183:3417–3427PubMedPubMedCentralGoogle Scholar
  19. Dixon DP, Skipsey M, Edwards R (2010) Roles for glutathione transferases in plant secondary metabolism. Phytochemistry 71:338–350PubMedGoogle Scholar
  20. Erdlenbruch BN, Kelly DP, Murrell JC (2001) Alkanesulfonate degradation by novel strains of Achromobacter xylosoxidans, Tsukamurella wratislaviensis and Rhodococcus sp., and evidence for an ethanesulfonate monooxygenase in A. xylosoxidans strain AE4. Arch Microbiol 176:406–414PubMedGoogle Scholar
  21. Fullam E, Westwood IM, Anderton MC, Lowe ED, Sim E, Noble MEM (2008) Divergence of cofactor recognition across evolution: coenzyme A binding in a prokaryotic arylamine N-acetyltransferase. J Mol Biol 375:178–191PubMedGoogle Scholar
  22. Gago G, Diacovich L, Arabolaza A, Tsai S-C, Gramajo H (2011) Fatty acid biosynthesis in actinomycetes. FEMS Microbiol Rev 35:475–497PubMedPubMedCentralGoogle Scholar
  23. Gao WT, Hou WD, Zheng MR, Tang LJ (2010) Clean and convenient one-pot synthesis of 4-hydroxycoumarin and 4-hydroxy-2-quinolinone derivatives. Synth Commun. CrossRefGoogle Scholar
  24. Gasteiger E, Hoogland C, Gattiker A, Duvaud SMW, Apel R, Bairoch A (2005) Protein identification and analysis tool on the ExPASy server. In: Walker JM (ed) The proteomic protocols handbook, Humana Press, New JerseyGoogle Scholar
  25. Gibson KJC, Gilleron M, Constant P, Brando T, Puzo G, Besra GS, Nigou J (2004) Tsukamurella paurometabola lipoglycan, a new lipoarabinomannan variant with pro-inflammatory activity. J Biol Chem 279:22973–22982PubMedGoogle Scholar
  26. Glenn AE, Bacon CW (2009) FDB2 encodes a member of the arylamine N-acetyltransferase family and is necessary for biotransformation of benzoxazolinones by Fusarium verticillioides. J Appl Microbiol 107:657–671PubMedGoogle Scholar
  27. Glenn AE, Karagianni EP, Ulndreaj A, Boukouvala S (2010) Comparative genomic and phylogenetic investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family. FEBS Lett 584:3158–3164PubMedGoogle Scholar
  28. Guex N, Peitsch MC, Schwede T (2009) Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis 30(Suppl 1):S162–S173PubMedPubMedCentralGoogle Scholar
  29. Hadasch A, Meunier B (1999) Oxidation of dichloroanilines and related anilides catalyzed by Iron(III) tetrasulfonatophthalocyanine. Eur J Inorg Chem 12:2319–2325Google Scholar
  30. Hall T (1999) BioEdit : a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41:95–98Google Scholar
  31. Hassanshahian M, Ahmadinejad M, Tebyanian H, Kariminik A (2013) Isolation and characterization of alkane degrading bacteria from petroleum reservoir waste water in Iran (Kerman and Tehran provenances). Mar Pollut Bull 73:300–305PubMedGoogle Scholar
  32. Hein DW, Boukouvala S, Grant DM, Minchin RF, Sim E (2008) Changes in consensus arylamine N-acetyltransferase gene nomenclature. Pharmacogenet Genomics 18:367–368PubMedPubMedCentralGoogle Scholar
  33. Hertweck C (2009) The biosynthetic logic of polyketide diversity. Angew Chem Int Ed Engl 48:4688–4716PubMedGoogle Scholar
  34. Hofstra AH (1994) Metabolism of hydralazine: relevance to drug-induced lupus. Drug Metab Rev 26:485–505PubMedGoogle Scholar
  35. Holton SJ, Dairou J, Sandy J, Rodrigues-Lima F, Dupret JM, Noble MEM, Sim E (2005) Structure of Mesorhizobium loti arylamine N-acetyltransferase 1. Acta Crystallogr F 61:14–16Google Scholar
  36. Huang J, Yan R, He J-Y, Wang P (2016) Purification and immobilization of a novel enantioselective lipase from Tsukamurella tyrosinosolvents for efficient resolution of ethyl 2-(2-oxopyrrolidin-1-yl) butyrate. Appl Biochem Biotechnol 180:609–622PubMedGoogle Scholar
  37. IARC (2010) IARC monographs on the evaluation of carcinogenic risks to humans. Some aromatic amines, organic dyes, and related exposures, vol 99. IARC, Lyon. CrossRefGoogle Scholar
  38. Karagianni EP, Kontomina E, Davis B, Kotseli B, Tsirka T, Garefalaki V, Sim E, Glenn AE, Boukouvala S (2015) Homologues of xenobiotic metabolizing N-acetyltransferases in plant-associated fungi: novel functions for an old enzyme family. Sci Rep 5:12900PubMedPubMedCentralGoogle Scholar
  39. Kawamura A, Graham J, Mushtaq A, Tsiftsoglou SA, Vath GM, Hanna PE, Wagner CR, Sim E (2005) Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol 69:347–359PubMedGoogle Scholar
  40. Kemmer G, Keller S (2010) Nonlinear least-squares data fitting in Excel spreadsheets. Nat Protoc 5:267–281PubMedGoogle Scholar
  41. Kettle AJ, Batley J, Benfield AH, Manners JM, Kazan K, Gardiner DM (2015) Degradation of the benzoxazolinone class of phytoalexins is important for virulence of Fusarium pseudograminearum towards wheat. Mol Plant Pathol 16:946–962PubMedPubMedCentralGoogle Scholar
  42. Klein DJ, Boukouvala S, McDonagh EM, Shuldiner SR, Laurieri N, Thorn CF, Altman RB, Klein TE (2016) PharmGKB summary: isoniazid pathway, pharmacokinetics. Pharmacogenet Genomics 26:436–444PubMedPubMedCentralGoogle Scholar
  43. Kubiak X, Dervins-Ravault D, Pluvinage B, Chaffotte AF, Gomez-Valero L, Dairou J, Busi F, Dupret J-M, Buchrieser C, Rodrigues-Lima F (2012) Characterization of an acetyltransferase that detoxifies aromatic chemicals in Legionella pneumophila. Biochem J 445:219–228PubMedGoogle Scholar
  44. Kubiak X, Li de la Sierra-Gallay I, Chaffotte AF, Pluvinage B, Weber P, Haouz A, Dupret J-M, Rodrigues-Lima F (2013) Structural and biochemical characterization of an active arylamine N-acetyltransferase possessing a non-canonical Cys-His-Glu catalytic triad. J Biol Chem 288:22493–22505PubMedPubMedCentralGoogle Scholar
  45. Kugler JH, Kraft A, Heissler S, Muhle-Goll C, Luy B, Schwack W, Syldatk C, Hausmann R (2015) Extracellular aromatic biosurfactant produced by Tsukamurella pseudospumae and T. spumae during growth on n-hexadecane. J Biotechnol 211:107–114PubMedGoogle Scholar
  46. Kugler JH, Muhle-Goll C, Kuhl B, Kraft A, Heinzler R, Kirschhofer F, Henkel M, Wray V, Luy B, Brenner-Weiss G, Lang S, Syldatk C, Hausmann R (2014) Trehalose lipid biosurfactants produced by the actinomycetes Tsukamurella spumae and T. pseudospumae. Appl Microbiol Biotechnol 98:8905–8915PubMedGoogle Scholar
  47. Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874PubMedPubMedCentralGoogle Scholar
  48. Lack NA, Kawamura A, Fullam E, Laurieri N, Beard S, Russell AJ, Evangelopoulos D, Westwood I, Sim E (2009) Temperature stability of proteins essential for the intracellular survival of Mycobacterium tuberculosis. Biochem J 418:369–378PubMedGoogle Scholar
  49. Letunic I, Bork P (2019) Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Marrakchi H, Laneelle M-A, Daffe M (2014) Mycolic acids: structures, biosynthesis, and beyond. Chem Biol 21:67–85PubMedGoogle Scholar
  51. Martins M, Pluvinage B, Li de la Sierra-Gallay I, Barbault F, Dairou J, Dupret J-M, Rodrigues-Lima F (2008) Functional and structural characterization of the arylamine N-acetyltransferase from the opportunistic pathogen Nocardia farcinica. J Mol Biol 383:549–560PubMedGoogle Scholar
  52. McDonagh EM, Boukouvala S, Aklillu E, Hein DW, Altman RB, Klein TE (2014) PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2. Pharmacogenet Genomics 24:409–425PubMedPubMedCentralGoogle Scholar
  53. Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, Weber T, Takano E, Breitling R (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346PubMedPubMedCentralGoogle Scholar
  54. Merino E, Barrientos A, Rodriguez J, Naharro G, Luengo JM, Olivera ER (2013) Isolation of cholesterol- and deoxycholate-degrading bacteria from soil samples: evidence of a common pathway. Appl Microbiol Biotechnol 97:891–904PubMedGoogle Scholar
  55. Monge A, Palop JA, Lopez de Cerain A, Senador V, Martinez-Crespo FJ, Sainz Y, Narro S, Garcia E, de Miguel C, Gonzalez M (1995) Hypoxia-selective agents derived from quinoxaline 1,4-di-N-oxides. J Med Chem 38:1786–1792PubMedGoogle Scholar
  56. Munk AC, Lapidus A, Lucas S, Nolan M, Tice H, Cheng J-F, Del Rio TG, Goodwin L, Pitluck S, Liolios K, Huntemann M, Ivanova N, Mavromatis K, Mikhailova N, Pati A, Chen A, Palaniappan K, Tapia R, Han C, Land M, Hauser L, Chang Y-J, Jeffries CD, Brettin T, Yasawong M, Brambilla E-M, Rohde M, Sikorski J, Goker M, Detter JC, Woyke T, Bristow J, Eisen JA, Markowitz V, Hugenholtz P, Kyrpides NC, Klenk H-P (2011) Complete genome sequence of Tsukamurella paurometabola type strain (no. 33). Stand Genomic Sci 4:342–351PubMedPubMedCentralGoogle Scholar
  57. Murinova S, Dercova K (2014) Response mechanisms of bacterial degraders to environmental contaminants on the level of cell walls and cytoplasmic membrane. Int J Microbiol 2014:873081PubMedPubMedCentralGoogle Scholar
  58. Nam S-W, Chun J, Kim S, Kim W, Zakrzewska-Czerwinska J, Goodfellow M (2003) Tsukamurella spumae sp. nov., a novel actinomycete associated with foaming in activated sludge plants. Syst Appl Microbiol 26:367–375PubMedGoogle Scholar
  59. Nam S-W, Kim W, Chun J, Goodfellow M (2004) Tsukamurella pseudospumae sp. nov., a novel actinomycete isolated from activated sludge foam. Int J Syst Evol Microbiol 54:1209–1212PubMedGoogle Scholar
  60. Niesen FH, Berglund H, Vedadi M (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2:2212–2221PubMedGoogle Scholar
  61. Notredame C, Higgins DG, Heringa J (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205–217Google Scholar
  62. Olson JB, Harmody DK, Bej AK, McCarthy PJ (2007) Tsukamurella spongiae sp. nov., a novel actinomycete isolated from a deep-water marine sponge. Int J Syst Evol Microbiol 57:1478–1481PubMedGoogle Scholar
  63. Ordaz-Guillen Y, Galindez-Mayer CJ, Ruiz-Ordaz N, Juarez-Ramirez C, Santoyo-Tepole F, Ramos-Monroy O (2014) Evaluating the degradation of the herbicides picloram and 2,4-D in a compartmentalized reactive biobarrier with internal liquid recirculation. Environ Sci Pollut Res Int 21:8765–8773PubMedGoogle Scholar
  64. Pathom-Aree W, Stach JEM, Ward AC, Horikoshi K, Bull AT, Goodfellow M (2006) Diversity of actinomycetes isolated from Challenger Deep sediment (10,898 m) from the Mariana Trench. Extremophiles 10:181–189PubMedGoogle Scholar
  65. Payton M, Auty R, Delgoda R, Everett M, Sim E (1999) Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance. J Bacteriol 181:1343–1347PubMedPubMedCentralGoogle Scholar
  66. Payton M, Mushtaq A, Yu TW, Wu LJ, Sinclair J, Sim E (2001) Eubacterial arylamine N-acetyltransferases—identification and comparison of 18 members of the protein family with conserved active site cysteine, histidine and aspartate residues. Microbiology 147:1137–1147PubMedGoogle Scholar
  67. Pereira L, Mondal PK, Alves M (2015) Aromatic amines sources, environmental impact and remediation. In: Lichtfouse E, Schwarzbauer J, Robert D (eds) Pollutants in buildings, water and living organisms. Springer International Publishing, Cham. CrossRefGoogle Scholar
  68. Pluvinage B, Dairou J, Possot OM, Martins M, Fouet A, Dupret J-M, Rodrigues-Lima F (2007) Cloning and molecular characterization of three arylamine N-acetyltransferase genes from Bacillus anthracis: identification of unusual enzymatic properties and their contribution to sulfamethoxazole resistance. Biochemistry 46:7069–7078PubMedGoogle Scholar
  69. Pluvinage B, Li de la Sierra-Gallay I, Kubiak X, Xu X, Dairou J, Dupret J-M, Rodrigues-Lima F (2011) The Bacillus anthracis arylamine N-acetyltransferase ((BACAN)NAT1) that inactivates sulfamethoxazole, reveals unusual structural features compared with the other NAT isoenzymes. FEBS Lett 585:3947–3952PubMedGoogle Scholar
  70. Ramakrishnan B, Venkateswarlu K, Sethunathan N, Megharaj M (2019) Local applications but global implications: can pesticides drive microorganisms to develop antimicrobial resistance? Sci Total Environ 654:177–189PubMedGoogle Scholar
  71. Robert X, Gouet P (2014) Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res 42:W320–W324PubMedPubMedCentralGoogle Scholar
  72. Rodrigues-Lima F, Dairou J, Diaz CL, Rubio MC, Sim E, Spaink HP, Dupret J-M (2006) Cloning, functional expression and characterization of Mesorhizobium loti arylamine N-acetyltransferases: rhizobial symbiosis supplies leguminous plants with the xenobiotic N-acetylation pathway. Mol Microbiol 60:505–512PubMedGoogle Scholar
  73. Rothman N, Garcia-Closas M, Hein DW (2007) Commentary: Reflections on G.M. Lower and colleagues’ 1979 study associating slow acetylator phenotype with urinary bladder cancer: meta-analysis, historical refinements of the hypothesis, and lessons learned. Int J Epidemiol 36:23–28PubMedGoogle Scholar
  74. Safaei S, Fatahi-Bafghi M, Pouresmaeil O (2018) Role of Tsukamurella species in human infections: first literature review. New Microbes New Infect. 22:6–12PubMedGoogle Scholar
  75. Saito K, Shinohara A, Kamataki T, Kato R (1985) Metabolic activation of mutagenic N-hydroxyarylamines by O-acetyltransferase in Salmonella typhimurium TA98. Arch Biochem Biophys 239:286–295PubMedGoogle Scholar
  76. Sandy J, Mushtaq A, Holton SJ, Schartau P, Noble MEM, Sim E (2005) Investigation of the catalytic triad of arylamine N-acetyltransferases: essential residues required for acetyl transfer to arylamines. Biochem J 390:115–123PubMedPubMedCentralGoogle Scholar
  77. Sandy J, Mushtaq A, Kawamura A, Sinclair J, Sim E, Noble M (2002) The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis—an enzyme which inactivates the anti-tubercular drug, isoniazid. J Mol Biol 318:1071–1083PubMedGoogle Scholar
  78. Sim E, Fakis G, Laurieri N, Boukouvala S (2012) Arylamine N-acetyltransferases—from drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention. Adv Pharmacol. CrossRefPubMedGoogle Scholar
  79. Sinclair JC, Sandy J, Delgoda R, Sim E, Noble ME (2000) Structure of arylamine N-acetyltransferase reveals a catalytic triad. Nat Struct Biol 7:560–564PubMedGoogle Scholar
  80. Soler A, Garcia-Hernandez J, Zornoza A, Alonso JL (2018) Diversity of culturable nocardioform actinomycetes from wastewater treatment plants in Spain and their role in the biodegradability of aromatic compounds. Environ Technol 39:172–181PubMedGoogle Scholar
  81. Steinhaus EA (1941) A study of the bacteria associated with thirty species of insects. J Bacteriol 42:757–790PubMedPubMedCentralGoogle Scholar
  82. Stratmann A, Toupet C, Schilling W, Traber R, Oberer L, Schupp T (1999) Intermediates of rifamycin polyketide synthase produced by an Amycolatopsis mediterranei mutant with inactivated rifF gene. Microbiology 145(Pt 1):3365–3375PubMedGoogle Scholar
  83. Suzuki H, Ohnishi Y, Horinouchi S (2007) Arylamine N-acetyltransferase responsible for acetylation of 2-aminophenols in Streptomyces griseus. J Bacteriol 189:2155–2159PubMedGoogle Scholar
  84. Taboada B, Estrada K, Ciria R, Merino E (2018) Operon-mapper: a web server for precise operon identification in bacterial and archaeal genomes. Bioinformatics 34:4118–4120PubMedPubMedCentralGoogle Scholar
  85. Taboada B, Verde C, Merino E (2010) High accuracy operon prediction method based on STRING database scores. Nucleic Acids Res 38:e130PubMedPubMedCentralGoogle Scholar
  86. Takenaka S, Cheng M, Mulyono Koshiya A, Murakami S, Aoki K (2009) Gene cloning and characterization of arylamine N-acetyltransferase from Bacillus cereus strain 10-L-2. J. Biosci Bioeng 107:27–32PubMedGoogle Scholar
  87. Tang Y, Teng JLL, Cheung CLW, Ngan AHY, Huang Y, Wong SSY, Yip EKT, Ng KHL, Que T-L, Lau SKP, Woo PCY (2016) Tsukamurella serpentis sp. nov., isolated from the oral cavity of Chinese cobras (Naja atra). Int J Syst Evol Microbiol 66:3329–3336PubMedGoogle Scholar
  88. Travkin V, Baskunov BP, Golovlev EL, Boersma MG, Boeren S, Vervoort J, van Berkel WJH, Rietjens IMCM, Golovleva LA (2002) Reductive deamination as a new step in the anaerobic microbial degradation of halogenated anilines. FEMS Microbiol Lett 209:307–312PubMedGoogle Scholar
  89. Tsirka T, Boukouvala S, Agianian B, Fakis G (2014) Polymorphism p.Val231Ile alters substrate selectivity of drug-metabolizing arylamine N-acetyltransferase 2 (NAT2) isoenzyme of rhesus macaque and human. Gene 536:65–73PubMedGoogle Scholar
  90. Tsirka T, Konstantopoulou M, Sabbagh A, Crouau-Roy B, Ryan A, Sim E, Boukouvala S, Fakis G (2018) Comparative analysis of xenobiotic metabolising N-acetyltransferases from ten non-human primates as in vitro models of human homologues. Sci Rep 8:9759PubMedPubMedCentralGoogle Scholar
  91. Tsukamura M, Kawakami K (1982) Lung infection caused by Gordona aurantiaca (Rhodococcus aurantiacus). J Clin Microbiol 16:604–607PubMedPubMedCentralGoogle Scholar
  92. Vagena E, Fakis G, Boukouvala S (2008) Arylamine N-acetyltransferases in prokaryotic and eukaryotic genomes: a survey of public databases. Curr Drug Metab 9:628–660PubMedGoogle Scholar
  93. Van Bogaert INA, Groeneboer S, Saerens K, Soetaert W (2011) The role of cytochrome P450 monooxygenases in microbial fatty acid metabolism. FEBS J 278:206–221PubMedGoogle Scholar
  94. Van der Geize R, Yam K, Heuser T, Wilbrink MH, Hara H, Anderton MC, Sim E, Dijkhuizen L, Davies JE, Mohn WW, Eltis LD (2007) A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages. Proc Natl Acad Sci USA 104:1947–1952PubMedGoogle Scholar
  95. Wan N, Tian J, Wang H, Tian M, He Q, Ma R, Cui B, Han W, Chen Y (2018) Identification and characterization of a highly S-enantioselective halohydrin dehalogenase from Tsukamurella sp. 1534 for kinetic resolution of halohydrins. Bioorg Chem 81:529–535PubMedGoogle Scholar
  96. Wang X, Yang S, Gu J, Deng J (2016) Mycobacterium tuberculosis arylamine N-acetyltransferase acetylates and thus inactivates para-aminosalicylic acid. Antimicrob Agents Chemother 60(12):7505–7508PubMedPubMedCentralGoogle Scholar
  97. Watanabe M, Sofuni T, Nohmi T (1992) Involvement of Cys69 residue in the catalytic mechanism of N-hydroxyarylamine O-acetyltransferase of Salmonella typhimurium. Sequence similarity at the amino acid level suggests a common catalytic mechanism of acetyltransferase for S. typhimurium and high. J Biol Chem 267:8429–8436PubMedGoogle Scholar
  98. Weber WW, Hein DW (1985) N-acetylation pharmacogenetics. Pharmacol Rev 37:25–79PubMedGoogle Scholar
  99. Weon H-Y, Yoo S-H, Anandham R, Schumann P, Kroppenstedt RM, Kwon S-W, Stackebrandt E (2010) Tsukamurella soli sp. nov., isolated from soil. Int J Syst Evol Microbiol 60:1667–1671PubMedGoogle Scholar
  100. Westwood IM, Holton SJ, Rodrigues-Lima F, Dupret J-M, Bhakta S, Noble MEM, Sim E (2005) Expression, purification, characterization and structure of Pseudomonas aeruginosa arylamine N-acetyltransferase. Biochem J 385:605–612PubMedPubMedCentralGoogle Scholar
  101. Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M (2018) DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 46:D1074–D1082Google Scholar
  102. Wu H, Dombrovsky L, Tempel W, Martin F, Loppnau P, Goodfellow GH, Grant DM, Plotnikov AN (2007) Structural basis of substrate-binding specificity of human arylamine N-acetyltransferases. J Biol Chem 282:30189–30197PubMedGoogle Scholar
  103. Wu K, Wang H, Sun H, Wei D (2015) Efficient kinetic resolution of phenyl glycidyl ether by a novel epoxide hydrolase from Tsukamurella paurometabola. Appl Microbiol Biotechnol 99:9511–9521PubMedGoogle Scholar
  104. Xu X, Li de la Sierra-Gallay I, Kubiak X, Duval R, Chaffotte AF, Dupret JM, Haouz A, Rodrigues-Lima F (2015) Insight into cofactor recognition in arylamine N-acetyltransferase enzymes: structure of Mesorhizobium loti arylamine N-acetyltransferase in complex with coenzyme A. Acta Crystallogr D 71:266–273PubMedGoogle Scholar
  105. Yao X-F, Khan F, Pandey R, Pandey J, Mourant RG, Jain RK, Guo J-H, Russell RJ, Oakeshott JG, Pandey G (2011) Degradation of dichloroaniline isomers by a newly isolated strain, Bacillus megaterium IMT21. Microbiology 157:721–726PubMedGoogle Scholar
  106. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL (2012) Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinform 13:134Google Scholar
  107. Yoon S-H, Ha S-M, Kwon S, Lim J, Kim Y, Seo H, Chun J (2017) Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int J Syst Evol Microbiol 67:1613–1617PubMedPubMedCentralGoogle Scholar
  108. Zang Y, Zhao S, Doll MA, States JC, Hein DW (2007) Functional characterization of the A411T (L137F) and G364A (D122N) genetic polymorphisms in human N-acetyltransferase 2. Pharmacogenet Genomics 17:37–45PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Vasiliki Garefalaki
    • 1
  • Evanthia Kontomina
    • 1
  • Charalambos Ioannidis
    • 1
  • Olga Savvidou
    • 1
  • Christina Vagena-Pantoula
    • 1
  • Maria-Giusy Papavergi
    • 1
  • Ioannis Olbasalis
    • 1
  • Dionysios Patriarcheas
    • 1
  • Konstantina C. Fylaktakidou
    • 1
  • Tamás Felföldi
    • 2
  • Károly Márialigeti
    • 2
  • Giannoulis Fakis
    • 1
  • Sotiria Boukouvala
    • 1
    Email author
  1. 1.Department of Molecular Biology and GeneticsDemocritus University of ThraceAlexandroupolisGreece
  2. 2.Department of MicrobiologyELTE Eötvös Loránd UniversityBudapestHungary

Personalised recommendations