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Construction of a doramectin producer mutant from an avermectin-overproducing industrial strain of Streptomyces avermitilis

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Abstract:

The avermectin analogue doramectin (CHC-B1), which is produced in mutants that have an altered biosynthesis pathway of avermectin, is one of the most effective agricultural pesticides and antiparasitics. We report here the construction of a bkdF olmA double-deletion mutant lacking one of the branched-chain α-keto acid dehydrogenase encoding genes (bkdF) and the oligomycin PKS encoding gene cluster (olmA) in Streptomyces avermitilis 76-05. We then characterized the production of various antibiotics in cultures of the deletion mutant. In a fermentation medium supplemented with cyclohexanecarboxylic acid, this double mutant produced doramectin and its analogues but no oligomycin. The mutant proved to be genetically stable, without any antibiotic resistance markers inserted into its chromosome, and could potentially become an industrial doramectin-producing strain after further improvement.

La doramectine (CHC-B1), un analogue de l’avermectine produit par les mutants dont la voie de biosynthèse de l’avermectine est modifiée, est un des pesticides et antiparasites les plus efficaces en agriculture. Nous rapportons ici la construction d’un double mutant de délétion bkdF olmA, déficient dans un des gènes codant une déshydrogénase spécifique des α-cétoacides à chaîne branchée (bkdF) et dans la batterie de gènes olmA codant la PKS d’oligomycine chez Streptomyces avermitilis 76-05. Nous avons ensuite caractérisé la production de divers antibiotiques en culture par le mutant de délétion. Ce double mutant produisait de la doramectine et son analogue dans un milieu de fermentation supplémenté avec de l’acide cyclohexane carboxylique, mais pas d’oligomycine. Ce mutant s’est avéré génétiquement stable, sans aucun marqueur chromosomique de résistance aux antibiotiques. Il pourrait potentiellement devenir une souche industrielle produisant de la doramectine suite à des améliorations additionnelles.

Document Type: Research Article

Publication date: December 1, 2009

More about this publication?
  • 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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