Microviridin 1777: A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach

Simon Sieber, Simone M. Grendelmeier, Lonnie A. Harris, Douglas A. Mitchell, Karl Gademann

Research output: Contribution to journalArticle

Abstract

The toxicity of the cyanobacterium Microcystis aeruginosa EAWAG 127a was evaluated against the sensitive grazer Thamnocephalus platyurus, and the extract possessed strong activity. To investigate the compounds responsible for cytotoxicity, a series of peptides from this cyanobacterium were studied using a combined genomic and molecular networking approach. The results led to the isolation, structure elucidation, and biological evaluation of microviridin 1777, which represents the most potent chymotrypsin inhibitor characterized from this family of peptides to date. Furthermore, the biosynthetic gene clusters of microviridin, anabaenopeptin, aeruginosin, and piricyclamide were located in the producing organism, and six additional natural products were identified by tandem mass spectrometry analyses. These results highlight the potential of modern techniques for the identification of natural products, demonstrate the ecological role of protease inhibitors produced by cyanobacteria, and raise ramifications concerning the presence of novel, yet uncharacterized, toxin families in cyanobacteria beyond microcystin.

Original languageEnglish (US)
Pages (from-to)438-446
Number of pages9
JournalJournal of Natural Products
Volume83
Issue number2
DOIs
StatePublished - Feb 28 2020

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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