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      Improved production of A40926 by Nonomuraea sp. through deletion of a pathway-specific acetyltransferase.

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          Abstract

          Nonomuraea strain ATCC 39727 produces the glycopeptide A40926, used for manufacturing dalbavancin, currently in advanced clinical trials. From the gene cluster involved in A40926 biosynthesis, a strain deleted in dbv23 was constructed. This mutant can produce only the glycopeptides lacking the O-linked acetyl residue at position 6 of the mannose moiety, while, under identical fermentation conditions, the wild-type strain produces mostly glycopeptides carrying an acetylated mannose. Furthermore, the total amount of glycopeptides produced by the mutant strain was found to be approximately twice that of the wild type. The reduced level of glycopeptides observed in the wild-type strain may be due to an inhibitory effect exerted by the acetylated compound on the biosynthesis of A40926. Indeed, spiking production cultures with > or =1 microg/ml of the acetylated glycopeptide inhibited A40926 production in the mutant strain.

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          Author and article information

          Journal
          Appl. Microbiol. Biotechnol.
          Applied microbiology and biotechnology
          Springer Nature America, Inc
          1432-0614
          0175-7598
          Aug 2010
          : 87
          : 5
          Affiliations
          [1 ] Vicuron Pharmaceuticals, 20140 Gerenzano, Italy. margherita.sosio@ktedogen.com
          Article
          10.1007/s00253-010-2579-2
          20414653

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