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

Thomas Garbe, Spiros Servos, Alastair Hawkins, George Dimitriadis, Douglas Young, Gordon Dougan, Ian Charles

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75 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalMolecular and General Genetics
Volume228
Issue number3
DOIs
Publication statusPublished - 1 Sep 1991
Externally publishedYes

Keywords

  • 3-Dehydroquinase
  • aro mutants
  • Dehydroquinate synthase
  • Mycobacterium tuberculosis
  • Quinic acid utilisation
  • Shikimate pathway

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