Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus. Author Yuchen Li, Seoung Lee, Esther Han, Mohammad Seyedsayamdost Publication Year 2022 Type Journal Article Abstract Natural products provide an important source of pharmaceuticals and chemical tools. Traditionally, assessment of unexplored microbial phyla has led to new natural products. However, with every new microbe, the number of orphan biosynthetic gene clusters (BGC) grows. As such, the more difficult proposition is finding new molecules from well-studied strains. Herein, we targeted Streptomyces rimosus, the widely-used oxytetracycline producer, for the discovery of new natural products. Using MALDI-MS-guided high-throughput elicitor screening (HiTES), we mapped the global secondary metabolome of S. rimosus and structurally characterized products of three cryptic BGCs, including momomycin, an unusual cyclic peptide natural product with backbone modifications and several non-canonical amino acids. We elucidated important aspects of its biosynthesis and evaluated its bioactivity. Our studies showcase HiTES as an effective approach for unearthing new chemical matter from "drained" strains. Keywords Multigene Family, Biological Products, Peptides, Cyclic, Amino Acids, Pharmaceutical Preparations, Oxytetracycline, Streptomyces rimosus Journal Angew Chem Int Ed Engl Volume 61 Issue 39 Pages e202208573 Date Published 2022 Sep 26 ISSN Number 1521-3773 DOI 10.1002/anie.202208573 Alternate Journal Angew Chem Int Ed Engl PMCID PMC9489664 PMID 35903822 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML