Identification of the Saquayamycin Gene Cluster in Streptomyces sp. KY40 – 1

A comparative genomic approach was taken to identify the Streptomyces sp. KY 40 – 1 gene cluster involved in the biosynthesis of saquayamycins H and I. Saquayamycins are angucycline antibiotics that possess antitumor activity. Saquayamycins H and I bear the unique aminosugar moiety rednose. Aminosugars are rare in angucyclines and are generally of great interest as they can increase the solubility of a drug and facilitate a stronger interaction between the drug and its target. The saquayamycin cluster will likely also reveal unique glycosyltransferases (GTs), including a C-GT, one targeting tertiary alcohol acceptors, and donor-substrate flexible GTs. Streptomyces sp. KY40 – 1 genomic DNA was sequenced and a BLAST analysis showed the closest similarity to the Sch 47554/Sch 47555 gene cluster of Streptomyces sp. SCC 2136. Deep sequencing of the region will reveal the gene cluster arrangement and allow a provisional assignment of gene product function. Gene disruption and PCR targeting will be used to define the biosynthetic pathway of rednose and a total enzymatic synthesis will follow for final confirmation. The identification of the genes encoding the biosynthetic pathway of saquayamycins H and I, particularly the rednose pathway and the glycosyltransferase genes are also attractive for future combinatorial biosynthetic manipulations of saccharide chain containing drugs.