A cryptic polyene biosynthetic gene cluster in Streptomyces calvus is expressed upon complementation with a functional bldA gene

Chem Biol. 2013 Oct 24;20(10):1214-24. doi: 10.1016/j.chembiol.2013.09.006. Epub 2013 Oct 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Amino Acid Sequence
  • Base Sequence
  • Gene Expression Regulation, Bacterial*
  • Genes, Bacterial / genetics*
  • Genetic Complementation Test*
  • Ligases / chemistry
  • Ligases / genetics
  • Ligases / metabolism
  • Molecular Sequence Data
  • Multigene Family*
  • Polyenes / metabolism*
  • Spores, Bacterial
  • Streptomyces / genetics*
  • Streptomyces / metabolism*
  • Streptomyces / physiology


  • Acyl Coenzyme A
  • Polyenes
  • Ligases