Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus.

TitleMomomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus.
Publication TypeJournal Article
Year of Publication2022
AuthorsLi, Y, Lee, SRak, Han, EJ, Seyedsayamdost, MR
JournalAngew Chem Int Ed Engl
Volume61
Issue39
Paginatione202208573
Date Published2022 Sep 26
ISSN1521-3773
KeywordsAmino 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>

DOI10.1002/anie.202208573
Alternate JournalAngew Chem Int Ed Engl
PubMed ID35903822
PubMed Central IDPMC9489664
Grant ListR01 GM140034 / GM / NIGMS NIH HHS / United States