Title | Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Li, Y, Lee, SRak, Han, EJ, Seyedsayamdost, MR |
Journal | Angew Chem Int Ed Engl |
Volume | 61 |
Issue | 39 |
Pagination | e202208573 |
Date Published | 2022 Sep 26 |
ISSN | 1521-3773 |
Keywords | Amino Acids, Biological Products, Multigene Family, Oxytetracycline, Peptides, Cyclic, Pharmaceutical Preparations, Streptomyces rimosus |
Abstract | <p>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.</p> |
DOI | 10.1002/anie.202208573 |
Alternate Journal | Angew Chem Int Ed Engl |
PubMed ID | 35903822 |
PubMed Central ID | PMC9489664 |
Grant List | R01 GM140034 / GM / NIGMS NIH HHS / United States |