TY - JOUR
T1 - Microviridin 1777
T2 - A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach
AU - Sieber, Simon
AU - Grendelmeier, Simone M.
AU - Harris, Lonnie A.
AU - Mitchell, Douglas A.
AU - Gademann, Karl
N1 - Publisher Copyright:
Copyright © 2020 American Chemical Society and American Society of Pharmacognosy.
PY - 2020/2/28
Y1 - 2020/2/28
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jnatprod.9b00986
DO - 10.1021/acs.jnatprod.9b00986
M3 - Article
C2 - 31989826
AN - SCOPUS:85080824103
SN - 0163-3864
VL - 83
SP - 438
EP - 446
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 2
ER -