Mining for new cancer fighters

Whether it’s on the isolated shores of Easter Island or on the more well-traversed terrain of a Japanese golf course, drug-producing bacteria have a penchant for popping up in some peculiar places. One of the latest locations is the acid drainage from an abandoned underground eastern Kentucky coal mine. Researchers led by the University of Kentucky’s Jon S. Thorson and Khaled A. Shaaban have found a strain of Streptomyces that produces 10 novel metabolites. Six of the compounds are new geldanamycins, and four of them are new cyclopentenone-containing ansamycin polyketides, dubbed mccrearamycins for McCreary County, where the bacterium was found (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201612447). Previous examples of geldanamycins are known to have anticancer activity via inhibition of heat shock protein 90 (Hsp90). When Thorson and Shaaban’s team tested the new geldanamycins in assays with Hsp90 and in cell tests, they found some of the new compounds also had anticancer activity. The chemists believe the mccrearamycins arise from benzylic acid rearrangement of the geldanamycins, suggesting a unique biosynthetic pathway.