Ascofuranone (AF)1 is a meroterpenoid with strong inhibitory activity against cyanide-insensitive alternative oxidases,2, 3, 4 and with therapeutic efficacy against rodent infection models of African trypanosomiasis5 and cryptosporidiosis.6 This promising drug candidate was initially found from nitrosoguanidine-induced mutant No. 34 of a soil fungus,1, 7 which had been identified as Ascochyta viciae Libert (Dothideomycetes; sometimes incorrectly spelled Ascochyta visiae). A structurally related compound, ascochlorin (AC), is produced by the same source,1, 8 although these compounds have significantly different effects on the mammalian respiratory chain.9 Therefore, cost-effective selective production is necessary to enable the use of AF as treatment against African trypanosomiasis, a neglected tropical disease that affects economically disadvantaged patients, many of whom may be unable to afford expensive treatments.

The mechanism of metabolic partitioning into AF and AC is an obvious key to achieving selective production. These compounds are supposed to be synthesized through prenylation of orsellinic acid and terminal cyclization via epoxidation,7, 10 but details of their biosynthesis have not been established. In theory, comparative genomics and transcriptomics of a set of closely related fungal strains that produce AF and AC at different ratios should help elucidate the biosynthetic pathway and the underlying genes. Although AF and AC derivatives have been reported from various distantly related filamentous fungi,7 they generally lack molecular information and thus no such set is available. In this light, we examined the original AF-producing strain and sought closely related strains as a first step toward elucidating the biosynthetic pathway.

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