A Cryptic Polyene Biosynthetic Gene Cluster in Streptomyces calvus Is Expressed upon Complementation with a Functional bldA Gene Academic Article uri icon

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abstract

  • Streptomyces calvus is best known as the producer of the fluorinated natural product nucleocidin. This strain of Streptomycetes is also unusual for displaying a "bald" phenotype that is deficient in the formation of aerial mycelium and spores. Genome sequencing of this organism revealed a point mutation in the bldA gene that is predicted to encode a misfolded Leu-tRNA(UUA) molecule. Complementation of S. calvus with a correct copy of bldA restored sporulation and additionally promoted production of a polyeneoic acid amide, 4-Z-annimycin, and a minor amount of the isomer, 4-E-annimycin. Bioassays reveal that these compounds inhibit morphological differentiation in other Actinobacteria. The annimycin gene cluster encoding a type 1 polyketide synthase was identified and verified through disruption studies. This study underscores the importance of the bldA gene in regulating the expression of cryptic biosynthetic genes.

authors

  • Kalan, Lindsay
  • Gessner, Arne
  • Thaker, Maulik N
  • Waglechner, Nicholas
  • Zhu, XiMing
  • Szawiola, Anjuli
  • Bechthold, Andreas
  • Wright, Gerard
  • Zechel, David L

publication date

  • October 2013