Gene ssfg_01967 (miaB) for tRNA modification influences morphogenesis and moenomycin biosynthesis in Streptomyces ghanaensis ATCC14672 Free

Abstract

Streptomyces ghanaensis ATCC14672 is remarkable for its production of phosphoglycolipid compounds, moenomycins, which serve as a blueprint for the development of a novel class of antibiotics based on inhibition of peptidoglycan glycosyltransferases. Here we employed mariner transposon (Tn) mutagenesis to find new regulatory genes essential for moenomycin production. We generated a library of 3000 mutants which were screened for altered antibiotic activity. Our focus centred on a single mutant, HIM5, which accumulated lower amounts of moenomycin and was impaired in morphogenesis as compared to the parental strain. HIM5 carried the Tn insertion within gene ssfg_01967 for putative tRNA (N6-isopentenyl adenosine(37)-C2)-methylthiotransferase, or MiaB, and led to a reduced level of thiomethylation at position 37 in the anticodon of S. ghanaensis transfer ribonucleic acid (tRNA). It is likely that the mutant phenotype of HIM5 stems from the way in which ssfg_01967::Tn influences translation of the rare leucine codon UUA in several genes for moenomycin production and life cycle progression in S. ghanaensis . This is the first report showing that quantitative changes in tRNA modification status in Streptomyces have physiological consequences.

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2018-12-13
2024-03-19
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References

  1. Makitrynskyy R, Rebets Y, Ostash B, Zaburannyi N, Rabyk M et al. Genetic factors that influence moenomycin production in streptomycetes. J Ind Microbiol Biotechnol 2010; 37:559–566 [View Article][PubMed]
    [Google Scholar]
  2. Ostash B, Saghatelian A, Walker S. A streamlined metabolic pathway for the biosynthesis of moenomycin A. Chem Biol 2007; 14:257–267 [View Article][PubMed]
    [Google Scholar]
  3. Gampe CM, Tsukamoto H, Doud EH, Walker S, Kahne D. Tuning the moenomycin pharmacophore to enable discovery of bacterial cell wall synthesis inhibitors. J Am Chem Soc 2013; 135:3776–3779 [View Article][PubMed]
    [Google Scholar]
  4. Mesleh MF, Rajaratnam P, Conrad M, Chandrasekaran V, Liu CM et al. Targeting bacterial cell wall peptidoglycan synthesis by inhibition of glycosyltransferase activity. Chem Biol Drug Des 2016; 87:190–199 [View Article][PubMed]
    [Google Scholar]
  5. Taylor JG, Li X, Oberthür M, Zhu W, Kahne DE. The total synthesis of moenomycin A. J Am Chem Soc 2006; 128:15084–15085 [View Article][PubMed]
    [Google Scholar]
  6. Fuse S, Tsukamoto H, Yuan Y, Wang TS, Zhang Y et al. Functional and structural analysis of a key region of the cell wall inhibitor moenomycin. ACS Chem Biol 2010; 5:701–711 [View Article][PubMed]
    [Google Scholar]
  7. Rabyk M, Ostash B, Rebets Y, Walker S, Fedorenko V. Streptomyces ghanaensis pleiotropic regulatory gene wblAgh influences morphogenesis and moenomycin production. Biotechnol Lett 2011; 33:2481–2486 [View Article][PubMed]
    [Google Scholar]
  8. Makitrynskyy R, Ostash B, Tsypik O, Rebets Y, Doud E et al. Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin. Open Biol 2013; 3:130121 [View Article][PubMed]
    [Google Scholar]
  9. Liu G, Chater KF, Chandra G, Niu G, Tan H. Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev 2013; 77:112–143 [View Article][PubMed]
    [Google Scholar]
  10. Antoraz S, Rico S, Rodríguez H, Sevillano L, Alzate JF et al. The orphan response regulator Aor1 is a new relevant piece in the complex puzzle of Streptomyces coelicolor antibiotic regulatory network. Front Microbiol 2017; 8:2444 [View Article][PubMed]
    [Google Scholar]
  11. Mutenko H, Makitrinskyy R, Tsypik O, Walker S, Ostash B et al. Genes for biosynthesis of butenolide-like signalling molecules in Streptomyces ghanaensis, their role in moenomycin production. Russ J Genet 2014; 50:563–568 [View Article][PubMed]
    [Google Scholar]
  12. Bilyk B, Weber S, Myronovskyi M, Bilyk O, Petzke L et al. In vivo random mutagenesis of streptomycetes using mariner-based transposon Himar1. Appl Microbiol Biotechnol 2013; 97:351–359 [View Article][PubMed]
    [Google Scholar]
  13. Koshla O, Lopatniuk M, Rokytskyy I, Yushchuk O, Dacyuk Y et al. Properties of Streptomyces albus J1074 mutant deficient in tRNALeuUAA gene bldA. Arch Microbiol 2017; 199:1175–1183 [View Article][PubMed]
    [Google Scholar]
  14. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA et al. Practical streptomyces Genetics Norwich, United Kingdom: John Innes Foundation; 2000
    [Google Scholar]
  15. Sambrook J, Russell DW. Molecular Cloning: a Laboratory Manual, 3rd ed. Cold Spring Harbor: NY: Cold Spring Harbor Laboratory; 2001
    [Google Scholar]
  16. Cayama E, Yépez A, Rotondo F, Bandeira E, Ferreras AC et al. New chromatographic and biochemical strategies for quick preparative isolation of tRNA. Nucleic Acids Res 2000; 28:E64 [View Article][PubMed]
    [Google Scholar]
  17. Ross R, Cao X, Yu N, Limbach PA. Sequence mapping of transfer RNA chemical modifications by liquid chromatography tandem mass spectrometry. Methods 2016; 107:73–78 [View Article][PubMed]
    [Google Scholar]
  18. Ostash B, Ostash I, Zhu L, Kharel MK, Luzhetskiĭ A et al. Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136. Genetika 2010; 46:604–609[PubMed]
    [Google Scholar]
  19. Beyer HM, Gonschorek P, Samodelov SL, Meier M, Weber W et al. AQUA cloning: a versatile and simple enzyme-free cloning approach. PLoS One 2015; 10:e0137652 [View Article][PubMed]
    [Google Scholar]
  20. Myronovskyi M, Welle E, Fedorenko V, Luzhetskyy A. Beta-glucuronidase as a sensitive and versatile reporter in actinomycetes. Appl Environ Microbiol 2011; 77:5370–5383 [View Article][PubMed]
    [Google Scholar]
  21. Lopatniuk M, Ostash B, Makitrynskyy R, Walker S, Luzhetskyy A et al. Testing the utility of site-specific recombinases for manipulations of genome of moenomycin producer Streptomyces ghanaensis ATCC14672. J Appl Genet 2015; 56:547–550 [View Article][PubMed]
    [Google Scholar]
  22. Esberg B, Leung HC, Tsui HC, Björk GR, Winkler ME. Identification of the miaB gene, involved in methylthiolation of isopentenylated A37 derivatives in the tRNA of Salmonella typhimurium and Escherichia coli. J Bacteriol 1999; 181:7256–7265[PubMed]
    [Google Scholar]
  23. Zheng C, Black KA, dos Santos PC. Diverse mechanisms of sulfur decoration in bacterial trna and their cellular functions. Biomolecules 2017; 7:E33 [View Article][PubMed]
    [Google Scholar]
  24. Rokytskyy I, Koshla O, Fedorenko V, Ostash B. Decoding options and accuracy of translation of developmentally regulated UUA codon in Streptomyces: bioinformatic analysis. Springerplus 2016; 5:982 [View Article][PubMed]
    [Google Scholar]
  25. Agris PF, Narendran A, Sarachan K, Väre VYP, Eruysal E. The importance of being modified: The role of rna modifications in translational fidelity. Enzymes 2017; 41:1–50 [View Article][PubMed]
    [Google Scholar]
  26. Pierrel F, Douki T, Fontecave M, Atta M. MiaB protein is a bifunctional radical-S-adenosylmethionine enzyme involved in thiolation and methylation of tRNA. J Biol Chem 2004; 279:47555–47563 [View Article][PubMed]
    [Google Scholar]
  27. Persson BC, Olafsson O, Lundgren HK, Hederstedt L, Björk GR. The ms2io6A37 modification of tRNA in Salmonella typhimurium regulates growth on citric acid cycle intermediates. J Bacteriol 1998; 180:3144–3151[PubMed]
    [Google Scholar]
  28. Lamichhane TN, Blewett NH, Crawford AK, Cherkasova VA, Iben JR et al. Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies in fission yeast. Mol Cell Biol 2013; 33:2918–2929 [View Article][PubMed]
    [Google Scholar]
  29. Zeharia A, Shaag A, Pappo O, Mager-Heckel AM, Saada A et al. Acute infantile liver failure due to mutations in the TRMU gene. Am J Hum Genet 2009; 85:401–407 [View Article][PubMed]
    [Google Scholar]
  30. Karlsborn T, Tükenmez H, Chen C, Byström AS. Familial dysautonomia (FD) patients have reduced levels of the modified wobble nucleoside mcm(5)s(2)U in tRNA. Biochem Biophys Res Commun 2014; 454:441–445 [View Article][PubMed]
    [Google Scholar]
  31. Morscher RJ, Ducker GS, Li SH, Mayer JA, Gitai Z et al. Mitochondrial translation requires folate-dependent tRNA methylation. Nature 2018; 554:128–132 [View Article][PubMed]
    [Google Scholar]
  32. Aubee JI, Olu M, Thompson KM. TrmL and TusA are necessary for rpoS and MiaA Is required for hfq expression in Escherichia coli. Biomolecules 2017; 7:39 [View Article][PubMed]
    [Google Scholar]
  33. Thompson KM, Gottesman S. The MiaA tRNA modification enzyme is necessary for robust RpoS expression in Escherichia coli. J Bacteriol 2014; 196:754–761 [View Article][PubMed]
    [Google Scholar]
  34. Aubee JI, Olu M, Thompson KM. The i6A37 tRNA modification is essential for proper decoding of UUX-Leucine codons during rpoS and iraP translation. RNA 2016; 22:729–742 [View Article][PubMed]
    [Google Scholar]
  35. Chater KF, Chandra G. The use of the rare UUA codon to define "expression space" for genes involved in secondary metabolism, development and environmental adaptation in Streptomyces. J Microbiol 2008; 46:1–11 [View Article][PubMed]
    [Google Scholar]
  36. Zaburannyy N, Ostash B, Fedorenko V. TTA Lynx: a web-based service for analysis of actinomycete genes containing rare TTA codon. Bioinformatics 2009; 25:2432–2433 [View Article][PubMed]
    [Google Scholar]
  37. Zinshteyn B, Gilbert WV. Loss of a conserved tRNA anticodon modification perturbs cellular signaling. PLoS Genet 2013; 9:e1003675 [View Article][PubMed]
    [Google Scholar]
  38. Armengod ME, Meseguer S, Villarroya M, Prado S, Moukadiri I et al. Modification of the wobble uridine in bacterial and mitochondrial tRNAs reading NNA/NNG triplets of 2-codon boxes. RNA Biol 2014; 11:1495–1507 [View Article][PubMed]
    [Google Scholar]
  39. Moukadiri I, Garzón MJ, Björk GR, Armengod ME. The output of the tRNA modification pathways controlled by the Escherichia coli MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species. Nucleic Acids Res 2014; 42:2602–2623 [View Article][PubMed]
    [Google Scholar]
  40. Chionh YH, McBee M, Babu IR, Hia F, Lin W et al. tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence. Nat Commun 2016; 7:13302 [View Article][PubMed]
    [Google Scholar]
  41. Chan CT, Deng W, Li F, Demott MS, Babu IR et al. Highly predictive reprogramming of tRNA modifications is linked to selective expression of codon-biased genes. Chem Res Toxicol 2015; 28:978–988 [View Article][PubMed]
    [Google Scholar]
  42. Hopwood DA. Genetic analysis and genome structure in Streptomyces coelicolor. Bacteriol Rev 1967; 31:373–403[PubMed]
    [Google Scholar]
  43. Gramajo HC, Takano E, Bibb MJ. Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated. Mol Microbiol 1993; 7:837–845 [View Article][PubMed]
    [Google Scholar]
  44. den Hengst CD, Tran NT, Bibb MJ, Chandra G, Leskiw BK et al. Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol 2010; 78:361–379 [View Article][PubMed]
    [Google Scholar]
  45. Pettersson BM, Kirsebom LA. tRNA accumulation and suppression of the bldA phenotype during development in Streptomyces coelicolor. Mol Microbiol 2011; 79:1602–1614 [View Article][PubMed]
    [Google Scholar]
  46. Lamichhane TN, Mattijssen S, Maraia RJ. Human cells have a limited set of tRNA anticodon loop substrates of the tRNA isopentenyltransferase TRIT1 tumor suppressor. Mol Cell Biol 2013; 33:4900–4908 [View Article][PubMed]
    [Google Scholar]
  47. Lawlor EJ, Baylis HA, Chater KF. Pleiotropic morphological and antibiotic deficiencies result from mutations in a gene encoding a tRNA-like product in Streptomyces coelicolor A3(2). Genes Dev 1987; 1:1305–1310 [View Article][PubMed]
    [Google Scholar]
  48. Leskiw BK, Mah R, Lawlor EJ, Chater KF. Accumulation of bldA-specified tRNA is temporally regulated in Streptomyces coelicolor A3(2). J Bacteriol 1993; 175:1995–2005 [View Article][PubMed]
    [Google Scholar]
  49. Kaminska KH, Baraniak U, Boniecki M, Nowaczyk K, Czerwoniec A et al. Structural bioinformatics analysis of enzymes involved in the biosynthesis pathway of the hypermodified nucleoside ms(2)io(6)A37 in tRNA. Proteins 2008; 70:1–18 [View Article][PubMed]
    [Google Scholar]
  50. Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B et al. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res 2018; 46:D303–D307 [View Article][PubMed]
    [Google Scholar]
  51. Hori H. Transfer RNA methyltransferases with a SpoU-TrmD (SPOUT) fold and their modified nucleosides in tRNA. Biomolecules 2017; 7:1
    [Google Scholar]
  52. Shepherd J, Ibba M. Bacterial transfer RNAs. FEMS Microbiol Rev 2015; 39:280–300 [View Article][PubMed]
    [Google Scholar]
  53. Väre VY, Eruysal ER, Narendran A, Sarachan KL, Agris PF. Chemical and conformational diversity of modified nucleosides affects tRNA structure and function. Biomolecules 2017; 7:29–32 [View Article][PubMed]
    [Google Scholar]
  54. Schweizer U, Bohleber S, Fradejas-Villar N. The modified base isopentenyladenosine and its derivatives in tRNA. RNA Biol 2017; 14:1197–1208 [View Article][PubMed]
    [Google Scholar]
  55. Ranjan N, Rodnina MV. Thio-modification of tRNA at the wobble position as regulator of the kinetics of decoding and translocation on the ribosome. J Am Chem Soc 2017; 139:5857–5864 [View Article][PubMed]
    [Google Scholar]
  56. Persson BC. Modification of tRNA as a regulatory device. Mol Microbiol 1993; 8:1011–1016 [View Article][PubMed]
    [Google Scholar]
  57. El Yacoubi B, Bailly M, de Crécy-Lagard V. Biosynthesis and function of posttranscriptional modifications of transfer RNAs. Annu Rev Genet 2012; 46:69–95 [View Article][PubMed]
    [Google Scholar]
  58. Luo Y, Huang H, Liang J, Wang M, Lu L et al. Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster. Nat Commun 2013; 4:2894–2909 [View Article][PubMed]
    [Google Scholar]
  59. Herrmann S, Siegl T, Luzhetska M, Petzke L, Jilg C et al. Site-specific recombination strategies for engineering actinomycete genomes. Appl Environ Microbiol 2012; 78:1804–1812 [View Article][PubMed]
    [Google Scholar]
  60. Huang J, Shi J, Molle V, Sohlberg B, Weaver D et al. Cross-regulation among disparate antibiotic biosynthetic pathways of Streptomyces coelicolor. Mol Microbiol 2005; 58:1276–1287 [View Article][PubMed]
    [Google Scholar]
  61. Myronovskyi M, Rosenkränzer B, Luzhetskyy A. Iterative marker excision system. Appl Microbiol Biotechnol 2014; 98:4557–4570 [View Article][PubMed]
    [Google Scholar]
  62. Karlsborn T, Tükenmez H, Mahmud AK, Xu F, Xu H et al. Elongator, a conserved complex required for wobble uridine modifications in eukaryotes. RNA Biol 2014; 11:1519–1528 [View Article][PubMed]
    [Google Scholar]
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