A cure for baldness and cryptic biosynthesis in Streptomyces calvus

Streptomyces calvus was first isolated by American Cyanamid in 1956 based on its ability to produce nucleocidin, a mimic of adenosine that contains unusual fluorine and sulfamate substituents. S. calvus also differs from most Streptomyces in its inability to form spores on solid media, giving colonies a 'bald' appearance. The genome sequence of S. calvus revealed the presence of a point mutation in the bldA gene, which is predicted to encode a misfolded and nonfunctional Leu-tRNA^UUA molecule. The bldA gene is well known to play a key role in sporulation and the expression of biosynthetic genes in Streptomyces. Upon complementation of S. calvus with a functional copy of the bldA gene, sporulation was restored and new secondary metabolites were observed in culture extracts. Recent work in identifying these new secondary metabolites and their cryptic biosynthetic genes will be presented.