Mithramycin is a natural product antibiotic/anticancer molecule produced by bacteria from the <i>Streptomyces</i> genus. Genetic engineering of the MTM biosynthetic pathway has led to the discovery of new analogues with improved anticancer activity. The M7W1 <i>S. argillaceus </i>mutant, which has the last enzyme in the biosynthetic pathway inactivated, produces three new MTM analogues of interest; MTM SK, MTM SDK, and MTM SA. MTM SK and MTM SDK show improved anti-cancer activity compared too native MTM, but MTM SA was largely discarded due to its decreased anti-cancer activity. Herein we attempt to restore the biological activity of MTM SA by modifying the critical aglycon side chain the MTM structure. Prior to modification, MTM SA must be isolated from a complex mixture, including the structurally similar MTM SK and MTM SDK. Isolation was achieved by taking advantage of the unique structural aspect of MTM SA and using a combination of solid phase extraction columns. After isolation, MTM SA was then modified in an attempt to restore and improve the anticancer activity, with preliminary results showing activity greater than that of MTM SK.

Isolation and modification of mithramycin SA

253rd National Meeting (2017)

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