S97: Withdrawn: Directed discovery of unknown natural products using fragment-based molecular barcodes

Natural products possess unique activities and are profoundly important as therapeutic and industrial agents. Microbial natural products are particularly notable for their diverse bioactivities and chemical structures, created by modular assembly-line like enzymes encoded by clusters of polyketide synthase and nonribosomal peptide synthetase genes. Genome sequencing suggests that many novel polyketides and nonribosomal peptides remain, but there is no direct method for their targeted isolation or for the generalized exploration of their pharmacophores and chemical space. Here, we describe an informatic strategy for automated, targeted detection of predicted or hypothetical natural products based on chemical barcodes and MS/MS fragmentation. Using this approach, we have identified over 25 new genetically-envisioned compounds and molecules with desired pharmacophores from complex extracts, leading to the selective isolation of over 10 novel structures. Through these examples, we demonstrate that our approach can enable navigation of natural product chemical space towards compounds with improved pharmacological properties.