Bioactive Natural Product Discovery via Deuterium Adduct Bioactivity Screening

Abstract

The discovery of bioactive natural products lies at the forefront of human medicine. The 20 continued discovery of these molecules is imperative in the fight against infection and disease. 21 While natural products have historically dominated the drug market, discovery in recent years has 22 slowed significantly, partly due to limitations in current discovery methodologies. This work 23 demonstrates a new workflow, Deuterium Adduct Bioactivity Screening (DABS), which pairs 24 untargeted isotope labeling with whole cell binding assays for bioactive natural product discovery. 25 DABS was validated and led to the discovery of a new isoprenyl guanidine alkaloid, zillamycin, 26 which showed anti-cancer and anti-microbial activities. DABS thus represents a new workflow to 27 accelerate discovery of natural products with a wide range of bioactive potential.