Garrett Deletti, Sajan Green, Caleb Weber, Amy Lane
Dr. Amy Lane | College of Arts and Sciences | Department of Biology
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.