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

Yuchen Li, Seoung Rak Lee, Esther J. Han, Mohammad R. Seyedsayamdost

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Article numbere202208573
JournalAngewandte Chemie - International Edition
Volume61
Issue number39
DOIs
StatePublished - Sep 26 2022

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry

Keywords

  • Biosynthesis
  • Cryptic Metabolites
  • HiTES
  • Natural Products
  • Non-Ribosomal Peptides

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