Journal
CHEMISTRY & BIOLOGY
Volume 20, Issue 10, Pages 1214-1224Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2013.09.006
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Funding
- Natural Sciences and Engineering Research Council (NSERC)
- Queen's University
- Ontario-Baden-Wurttemberg Faculty Research Exchange Program
- Canadian Institutes of Health Research (CIHR) [MT-14981]
- Canada Research Chairs Program
- CIHR Canada graduate scholarship
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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.
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