Three unlinked gene clusters are involved in clavam metabolite biosynthesis in Streptomyces clavuligerus

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Abstract:

In Streptomyces clavuligerus, three groups of genes are known to be involved in the biosynthesis of the clavam metabolites. Since antibiotic biosynthetic genes are invariably clustered on the chromosome in prokaryotes, chromosome walking was undertaken in an attempt to show that the three groups of clavam genes would resolve into a single super-cluster when analyzed at larger scale. However, no evidence of linkage between the three groups was obtained. Furthermore, Southern analysis of macro-restriction fragments of genomic DNA separated by pulsed-field gel electrophoresis also indicated that the three groups of genes are not linked. Despite the structural and biosynthetic relatedness of the clavam metabolites, our results suggest that the genes involved in their production lie in three unlinked gene clusters. We believe that this represents the first instance in bacteria of genes involved in the biosynthesis of a single family of antibiotics sharing a common biosynthetic pathway and yet residing in three separate locations on the chromosome.Key words: Streptomyces, clavulanic acid, clavams, paralogues, gene clusters.

Chez Streptomyces clavuligerus, trois groupes de gènes sont impliqués dans la biosynthèse des clavames. Puisque les gènes impliqués dans la biosynthèse d'antibiotiques sont invariablement agrégés sur le chromosome des procaryotes, une marche chromosomique a été entreprise afin de démontrer que les trois groupes de gènes impliqués dans la synthèse des clavames se résolvent dans un seul super agrégat lorsque analysés à grande échelle. Cependant, aucune évidence de liaison entre ces trois groupes de gènes ne fut obtenue. Qui plus est, des analyses par Southern de larges fragments de restriction de l'ADN génomique séparés par chromatographie en champ pulsé indiquent également que ces trois groupes de gènes ne sont pas liés. Malgré les relations structurelles et biosynthétiques des clavames, nos résultats démontrent que les gènes impliqués dans leur production se retrouvent dans trois agrégats non reliés. Nous croyons que ceci représente le premier exemple, chez la bactérie, de gènes impliqués dans la biosynthèse d'une famille unique d'antibiotiques qui partagent une voie métabolique commune, et qui sont localisés en trois endroits séparés sur le chromosome.Mots clés : Streptomyces, acide clavulinique, clavames, paralogues, agrégats de gènes.[Traduit par la Rédaction]

Document Type: Research Article

Publication date: October 1, 2004

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  • Published since 1954, this monthly journal contains new research in the field of microbiology including applied microbiology and biotechnology; microbial structure and function; fungi and other eucaryotic protists; infection and immunity; microbial ecology; physiology, metabolism and enzymology; and virology, genetics, and molecular biology. It also publishes review articles and notes on an occasional basis, contributed by recognized scientists worldwide.
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