The Mycobacterium tuberculosis shikimate pathway genes: Evolutionary relationship between biosynthetic and catabolic 3-dehydroquinases |
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Authors: | Thomas Garbe Spiros Servos Alastair Hawkins George Dimitriadis Douglas Young Gordon Dougan and Ian Charles |
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Institution: | (1) MRC Tuberculosis and Related Infections Unit, RPMS, Hammersmith Hospital, Ducane Road, W12 0HS London, UK;(2) Department of Cell Biology, Wellcome Research Laboratories, BR3 3BS Langley Park, Beckenham, Kent, UK;(3) Department of Biochemistry and Genetics, Catherine Cookson Building, Medical School, University of Newcastle upon Tyne, NE2 4HH, UK;(4) Department of Biology, University of Patras, 26500 Patras, Greece |
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Abstract: | 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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Keywords: | aro mutants Dehydroquinate synthase 3-Dehydroquinase Mycobacterium tuberculosis Quinic acid utilisation Shikimate pathway |
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