Cytochrome P450 monooxygenase; part of the asc-1 gene cluster that mediates the biosynthesis of both ascochlorin and ascofuranone, a strong inhibitor of cyanide-insensitive alternative oxidases and a promising drug candidate against African trypanosomiasis. The first step in the pathway is performed by the non-reducing polyketide synthase ascC that produces orsellinic acid by condensing acetyl-CoA with 3 malonyl-CoA units. Orsellinic acid is then prenylated by the prenyltransferase ascA to yield ilicicolinic acid B. Ilicicolinic acid B is further reduced to ilicicolin B by the reductase ascB. The halogenase ascD then chlorinates ilicicolin B to produce ilicicolin A which is converted to ilicicolin A epoxide by the cytochrome P450 monooxygenase ascE that catalyzes stereoselective epoxidation of the terminal double bond of the prenyl group. Ilicicolin A epoxide is the last common precursor for the biosynthesis of ascofuranone and ascochlorin. The terpene cyclase ascF produces a monocyclic terpene, and the cyclization reaction is proposed to be initiated by protonation of the terminal epoxide of ilicicolin A epoxide to generate a monocyclic tertiarycation, which is followed by a series of hydride and methyl shifts with abstraction of proton, leading to the formation of the (14S,15R,19R)-trimethylcyclohexanone ring structure of ilicicolin C, which is finally reduced to ascochlorin by the dehydrogenase ascG. On the other hand, ilicicolin A epoxide is hydroxylated by the cytochrome P450 monooxygenase ascH, and the resultant product is cyclized by the terpene cyclase ascI to ascofuranol via protonation-initiated epoxide ring opening, which facilitates the 6-endo-tet cyclization to form the tetrahy-drofuran ring. Finally, ascofuranol is oxidized into ascofuranone by ascJ