The Cyanobacterial 'Nutraceutical' Phycocyanobilin Inhibits Cysteine Protease Legumain

Autor: Isabel V. L. Wilkinson, Gabriel Castro‐Falcón, Maria C. Roda‐Serrat, Trevor N. Purdy, Jan Straetener, Melanie M. Brauny, Lisa Maier, Heike Brötz‐Oesterhelt, Lars P. Christensen, Stephan A. Sieber, Chambers C. Hughes
Rok vydání: 2023
Předmět:
Zdroj: ChemBioChem. 24
ISSN: 1439-7633
1439-4227
Popis: The blue biliprotein phycocyanin, produced by photoautotrophic cyanobacteria including spirulina (Arthrospira) and marketed as a natural food supplement or "nutraceutical," is reported to have anti-inflammatory, antioxidant, immunomodulatory and anti-cancer activity. These diverse biological activities have been specifically attributed to the phycocyanin chromophore, phycocyanobilin (PCB). However, the mechanism of action of PCB and the molecular targets responsible for the beneficial properties of PCB are not well understood. We developed a procedure to rapidly cleave the PCB pigment from phycocyanin using an ethanolysis reaction and then characterized it as an electrophilic natural product that interacts covalently with thiol nucleophiles but lacked any appreciable cytotoxicity or antibacterial activity against common pathogens and gut microbes. We then designed alkyne-bearing PCB probes for use in chemical proteomics target deconvolution studies. Target identification and validation revealed the cysteine protease legumain (aka asparaginyl endopeptidase, AEP) as a target of PCB, which was inhibited with an IC50 of 65 ± 8 µM, and thus may account for PCB's diverse reported biological activities.
Databáze: OpenAIRE
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