Targeted Discovery of Cryptic Metabolites with Antiproliferative Activity. Author Esther Han, Seoung Lee, Shotaro Hoshino, Mohammad Seyedsayamdost Publication Year 2022 Type Journal Article Abstract Microorganisms have provided a rich source of therapeutically valuable natural products. Recent advances in whole genome sequencing and bioinformatics have revealed immense untapped potential for new natural products in the form of silent or "cryptic" biosynthetic genes. We herein conducted high-throughput elicitor screening (HiTES) in conjunction with cytotoxicity assays against selected cancer cell lines with the goal of uncovering otherwise undetectable cryptic metabolites with antiproliferative activity. Application to facilitated identification of clavamates A and B, two bioactive metabolites with unusual structural features, as well as facile activation of a gene cluster coding for tunicamycin, which exhibited strong growth-inhibitory activity. The elicitor we identified was pleiotropic, additionally leading to the discovery of a modified, bicyclic pentapeptide natural product. Our results highlight the utility of this approach in identifying new molecules with antiproliferative activity from even overexploited microbial strains. Keywords Anti-Bacterial Agents, Computational Biology, High-Throughput Screening Assays, Multigene Family, Biological Products Journal ACS Chem Biol Volume 17 Issue 11 Pages 3121-3130 Date Published 2022 Nov 18 ISSN Number 1554-8937 DOI 10.1021/acschembio.2c00588 Alternate Journal ACS Chem Biol PMID 36228140 PubMedGoogle ScholarBibTeXEndNote X3 XML