Latest Publications
Early Steps of the Biosynthesis of the Anticancer Antibiotic Pleurotin
Jack A. Weaver, Duha Alkhder, Panward Prasongpholchai, Michaël D. Tadesse, Emmanuel L. de los Santos, Lijiang Song, Christophe Corre, Fabrizio Alberti
Pleurotin is a meroterpenoid specialized metabolite made by the fungus Hohenbuehelia grisea, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has been achieved, including through a stereoselective route; however, its biosynthesis has not been characterized. In this study, we used isotope-labeled precursor feeding to show that the nonterpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimize their production for therapeutic use and engineer the pathway toward the biosynthesis of valuable analogues.