Manipulation of Cellular Machinery to Produce Anti-cancer Drugs

Research Authorship:

Garrett Deletti, Sajan Green, Caleb Weber, Amy Lane

Faculty Mentor:

Dr. Amy Lane | College of Arts and Sciences | Department of Biology

Abstract:

The nocardioazine natural products are uniquely prenylated and methylated indole alkaloid diketopiperazines (DKPs) that reverse drug resistance of cancer cell lines. We unveiled the nocardioazine biosynthetic pathway from a marine actinomycete, demonstrating that a cyclodipeptide synthase catalyzes cyclo(L-Trp-L-Trp) DKP precursor formation followed by tailoring of this DKP via a novel racemase, prenyltransferase, and methyltransferase to yield nocardioazine B. These results highlight the aptitude of bacteria for chemical synthesis and offer new enzymatic tools for crafting complex organic molecules.