Genome Mining Reveals the Biosynthesis of Sativene and Its Oxidative Conversion to seco -Sativene.

Sativene ( 1 ) and seco -sativene are an important family of fungal sesquiterpenoids that feature unique tricyclo[4.4.0.0 1,7 ]decane and bicyclo[3.2.1]octane skeletons, respectively. Herein, we identify a three-enzyme cassette: SatA cyclizes farnesyl diphosphate (FPP) to form compound 1 ; CYP450 SatB catalyzes C14-C15 dihydroxylations and subsequent bond cleavage; and reductase SatC regioselectively reduces C14 aldehyde and mediates hemiacetal ring closure to generate prehelminthosporol ( 2 ). Our findings clarify the synthetic step of sativene and its oxidative transformation processes into seco -sativene.