Alpha-humulene synthase; part of the gene cluster that mediates the biosynthesis of eupenifeldin, a bistropolone meroterpenoid that acts as an antitumor agent (PubMed:30980906). The first step of eupenifeldin biosynthesis is the biosynthesis of 3-methylorcinaldehyde performed by the non-reducing polyketide synthase eupA (PubMed:30980906). Oxidative dearomatization of 3-methylorcinaldehyde likely catalyzed by the FAD-dependent monooxygenase eupB is followed by oxidative ring expansion by the 2-oxoglutarate-dependent dioxygenase eupC to provide the first tropolone metabolite, tropolone stipitaldehyde (Probable). In parallel, generation of sesquiterpene alpha-humulene from farnesylpyrophosphate (FPP) is catalyzed by the terpene cyclase eupE (PubMed:30980906). The cytochrome P450 monooxygenase eupD then hydroxylates humulene to humulenol (PubMed:30980906). The putative Diels-Alderase eupF probably catalyzes the formation of the tropolone-humulene skeleton by linking humulenol and the polyketide moiety (Probable). The short-chain dehydrogenase/reductase eupG and the flavin-dependent monooxygenase eupH are also essential for eupenifeldin biosynthesis and are likely the additional decorating enzymes of the tropolone-humulene skeleton to produce final eupenifeldin or derivatives (Probable). (2E,6E)-farnesyl diphosphate = alpha-humulene + diphosphate Secondary metabolite biosynthesis; terpenoid biosynthesis. Abolishes the production of humulene. Eupenifeldin is a bistropolone-humulene meroterpenoid first discovered as an antitumor and anti-leukemia agent (PubMed:8360103). This metabolite shows also anthelmintic activity against the parasitic worm Hemonchus contortus, anti-malarial activity as well as antifungal activity (PubMed:18095654, Ref.4). Belongs to the terpene synthase family. Alpha-humulene synthase eupE subfamily.