Resolution of the ABA Biosynthesis Controversy: Discovery of a Dihydroxylating Terpene Synthase and Its Convergent...

Fungal terpene biosynthesis is a vital source of bioactive metabolites. Here, we elucidate the function of BcStc5, a Botrytis cinerea terpene synthase previously linked to abscisic acid (ABA) biosynthesis. Using bioinformatics and heterologous expression, we demonstrate that BcStc5 catalyzes the formation of (4S,5S,7R,10S)-4β,10α-eudesmane-5β,11-diol (1), a dihydroxylated sesquiterpenoid not previously reported in fungi. Mechanistic modeling suggests BcStc5 employs a novel, P450-independent dihydroxylation strategy. We further established a scalable bioproduction platform in Escherichia coli, achieving titers >550 mg/L. This work resolves a long-standing biosynthetic controversy, characterizing BcStc5 as an eudesmanediol synthase rather than the ABA cyclase, settling the controversy over this protein.