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The Mycobacterium tuberculosis shikimate pathway genes: Evolutionary relationship between biosynthetic and catabolic 3-dehydroquinases

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Summary

The Mycobacterium tuberculosis shikimate pathway genes designated aroB and aroQ encoding 3-dehydroquinate synthase and 3-dehydroquinase, respectively were isolated by molecular cloning and their nucleotide sequences determined. The deduced dehydroquinate synthase amino acid sequence from M. tuberculosis showed high similarity to those of equivalent enzymes from prokaryotes and filamentous fungi. Surprisingly, the deduced M. tuberculosis 3-dehydroquinase amino acid sequence showed no similarity to other characterised prokaryotic biosynthetic 3-dehydroquinases (bDHQases). A high degree of similarity was observed, however, to the fungal catabolic 3-dehydroquinases (cDHQases) which are active in the quinic acid utilisation pathway and are isozymes of the fungal bDHQases. This finding indicates a common ancestral origin for genes encoding the catabolic dehydroquinases of fungi and the biosynthetic dehydroquinases present in some prokaryotes. Deletion of genes encoding shikimate pathway enzymes represents a possible approach to generation of rationally attenuated strains of M. tuberculosis for use as live vaccines.

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References

  • Beri R-K, Grant S, Roberts CF, Smith M, Hawkins AR (1990) Selective overexpression of the QutE gene encoding catabolic 3-dehydroquinase in multicopy transformants of A. nidulans. Biochem J 265:337–342

    Google Scholar 

  • Biggin MD, Gibson TS, Hong CF (1983) Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci USA 86:3963–3965

    Google Scholar 

  • Charles IG, Keyte JW, Brammar WJ, Hawkins AR (1985) Nucleotide sequence encoding the biosynthetic dehydroquinase function of the pentafunctional AROM locus of Aspergillus nidulans. Nucleic Acids Res 13:8119–8128

    Google Scholar 

  • Charles IG, Keyte JW, Brammar WJ, Smith M, Hawkins AR (1986) The isolation and nucleotide sequence of the complex AROM locus of Aspergillus nidulans. Nucleic Acids Res 14:2201–2213

    Google Scholar 

  • Collins FM (1974) Vaccines and cell-mediated immunity. Bacteriol Rev 38:371–402

    Google Scholar 

  • Da Silva AJS, Whittington H, Clements J, Roberts CF, Hawkins AR (1986) Sequence analysis and transformation by the catabolic 3-dehydroquinase (QUTE) gene from Aspergillus nidulans. Biochem J 240:481–488

    Google Scholar 

  • DeFeyter RC, Davidson BE, Pittard J (1986) Nucleotide sequence of the transcription unit containing the aroL and aroM genes from Escherichia coli K-12. J Bacteriol 165:233–239

    Google Scholar 

  • Dougan G, Sherratt DJ (1977) Tna as a probe for the structure and function of ColE1. Mol Gen Genet 151:151–160

    Google Scholar 

  • Dougan G, Maskell D, Pickard D, Hormaeche C (1987) Isolation of stable aroA mutants of Salmonella typhi Ty2: properties and preliminary characterisation in mice. Mol Gen Genet 207:402–405

    Google Scholar 

  • Duncan K, Chaudhuri S, Campbell MS, Coggins JR (1986) The overexpression and complete amino acid sequence of Escherichia coli 3-dehydroquinase. Biochem J 238:475–483

    Google Scholar 

  • Duncan K, Edwards RM, Coggins JR (1987) The penta functional arom enzyme of Saccharomyces cerevisiae is a mosaic of monofunctional domains. Biochem J 246:375–386

    Google Scholar 

  • Engers HD, Workshop Participants (1985) Results of a World Health Organisation sponsored workshop on monoclonal antibodies to Mycobacterium leprae. Infect Immun 48:718–720

    Google Scholar 

  • Engers HD, Workshop Participants (1986) Results of a World Health Organisation sponsored workshop to characterise antigens recognised by mycobacteria-specific monoclonal antibodies. Infect Immun 51:718–720

    Google Scholar 

  • Fine PEM (1988) BCG vaccination against tuberculosis and leprosy. Br Med Bull 44:691–703

    Google Scholar 

  • Garbe T, Jones C, Charles I, Dougan G, Young D (1990) Cloning and characterisation of the aroA gene from Mycobacterium tuberculosis. J Bacteriol 172:6774–6782

    Google Scholar 

  • Grant S, Roberts CF, Lamb H, Stout M, Hawkins AR (1988) Genetic regulation of the quinic acid utilisation (QUT) gene cluster in Aspergillus nidulans. J Gen Microbiol 134:347–358

    Google Scholar 

  • Hawkins AR (1987) The complex AROM locus of Aspergillus nidulans: evidence for multiple gene fusions and convergent evolution. Curr Genet 11:491–498

    Google Scholar 

  • Hawkins AR, Roberts CF (1989) In: Nevalainen H, Pentilla M (eds) Molecular biology of filamentous fungi, vol 6. Foundation for Biotechnical and Industrial Fermentation Research, Helsinki, Finland, pp 85–100

    Google Scholar 

  • Hawkins AR, Smith M (1991) Domain structure and interaction within the pentafunctional arom polypeptide. Eur J Biochem 196:717–724

    Google Scholar 

  • Hawkins AR, Giles NH, Kinghorn JR (1982a) Genetic and biochemical aspects of quinate breakdown in the filamentous fungus Aspergillus nidulans. Biochem Genet 20:271–286

    Google Scholar 

  • Hawkins AR, Reinert WR, Giles NH (1982b) Characterization of Neurospora crassa catabolic dehydroquinase purified from N. crassa and Escherichia coli. Biochem J 203:769–773

    Google Scholar 

  • Hawkins AR, Da Silva AJS, Roberts CF (1984) Evidence for two control genes regulating expression of the quinic acid utilisation (QUT) gene cluster in Aspergillus nidulans. J Gen Microbiol 130:567–574

    Google Scholar 

  • Hoch JA, Nester EW (1973) Gene-enzyme relationships of aromatic acid biosynthesis in Bacillus subtilis. J Bacteriol 116:59–66

    Google Scholar 

  • Horowitz NH (1965) In: Bryson B and Vogel HJ (eds) Evolving genes and proteins. Academic Press, New York, pp 15–23

    Google Scholar 

  • Husson RN, James BE, Young RA (1990) Gene replacement and expression of foreign DNA in mycobacteria. J Bacteriol 172:519–524

    Google Scholar 

  • Kinghorn JR, Hawkins AR (1982) Cloning and expression in Escherichia coli K12 of the biosynthetic dehydroquinase function of the AROM gene cluster from the eukaryote Aspergillus nidulans. Mol Gen Genet 186:145–152

    Google Scholar 

  • Martin C, Timm J, Rauzier J, Gomez-Lus R, Davies J, Gicquel B (1990) Transposition of an antibiotic resistance element in mycobacteria. Nature 345:739–743

    Google Scholar 

  • Millar C, Coggins JR (1986) The complete amino acid sequence of 3-dehydroquinase synthase of Escherichia coli K12. FEBS Lett 200:11–17

    Google Scholar 

  • O'Callaghan D, Maskell D, Liew FY, Easmon CSF, Dougan G (1988) Characterisation of aromatic and purine-dependent Salmonella typhimurium: attenuation, persistence, and ability to induce protective immunity in Balb/c mice. Infect Immun 56:419–423

    Google Scholar 

  • Pittard J, Wallace BJ (1966) Distribution and function of genes concerned with aromatic biosynthesis in Escherichia coli. J Bacteriol 91:1494–1508

    Google Scholar 

  • Sanger F, Michelin S, Coulson AR (1977) DNA sequencing with chain-termination inhibitors. Proc Natl Acad Sci USA 74:5463–5467

    CAS  PubMed  Google Scholar 

  • Snapper SB, Lugosi L, Jekkel A, Melton RE, Kieser T, Bloom BR, Jacobs WR (1988) Lysogeny and transformation in mycobacteria: stable expression of foreign genes. Proc Natl Acad Sci USA 85:6987–6991

    Google Scholar 

  • Styblo K (1989) Overview and epidemilogic assessment of the current global tuberculosis situation with an emphasis on control in developing countries. Rev Infect Dis 11, suppl 2:S339-S346

    Google Scholar 

  • Tabor S, Richardson CC (1987) DNA sequencing analysis with a modified bacteriophage T7 polymerase. Proc Natl Acad Sci USA 84:4767–4771

    Google Scholar 

  • White PJ, Young J, Hunter TS, Nimmo HG, Coggins JR (1990) The purification and characterization of 3-dehydroquinase from Streptomyces coelicolor. Biochem J 265:735–738

    Google Scholar 

  • Young DB (1988) Structure of mycobacterial antigens. Br Med Bull 44:4767–4771

    Google Scholar 

  • Young RA, Bloom BR, Grosskinsky CM, Ivanyi J, Thomas D, Davis RW (1985a) Dissecting Mycobacterium tuberculosis antigens using recombinant DNA. Proc Natl Acad Sci USA 82:2583–2587

    Google Scholar 

  • Young RA, Mehra V, Sweetser D, Buchanan T, Clark-Curtiss J, Davis RW, Bloom BR (1985b) Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae. Nature 316:450–452

    Google Scholar 

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Communicated by J. Gajewski

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Garbe, T., Servos, S., Hawkins, A. et al. The Mycobacterium tuberculosis shikimate pathway genes: Evolutionary relationship between biosynthetic and catabolic 3-dehydroquinases. Molec. Gen. Genet. 228, 385–392 (1991). https://doi.org/10.1007/BF00260631

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  • DOI: https://doi.org/10.1007/BF00260631

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