Biosynthesis of aphidicolin proceeds via the mevalonate pathway in the endophytic fungus Nigrospora sphaerica

We have previously identified the endophytic fungus Nigrospora sphaerica as a prolific producer of the bioactive diterpene aphidicolin. Herein we report a study to establish the best conditions for the production of aphidicolin by N. sphaerica in Czapek medium. The sugar source (glucose and sucrose) and the incubation time (4-15 days) were optimized for further application on biosynthetic studies of the diterpene. The highest levels of production of aphidicolin were found on the 8th day with 1%-glucose and on the 12th day with 3%-sucrose based media. The biosynthesis of aphidicolin was investigated using [1-13C]-D-glucose as a precursor, and showed that the isoprene units of aphidicolin are derived from the mevalonate pathway.