Scytalone dehydratase (SD)

Scytalone dehydratase is an enzyme (EC 4.2.1.94) in the lyase family, specifically classified as a hydro-lyase, that catalyzes the dehydration of scytalone to 1,3,8-trihydroxynaphthalene as a critical step in the biosynthesis of dihydroxynaphthalene (DHN) melanin in fungi[2][9]. This enzyme is essential for the pathogenicity of certain phytopathogenic fungi, most notably *Magnaporthe grisea* (now *Pyricularia oryzae*), which causes rice blast disease—a major threat to rice cultivation[5][6][9]. Scytalone dehydratase is a trimeric protein, with each subunit comprising about 129 amino acids and adopting a cone-shaped alpha + beta barrel that encloses a hydrophobic active site[1][6]. It serves as a validated molecular target for antifungal drug design, with inhibitors such as carpropamid directly binding to and blocking the enzyme, resulting in inhibition of fungal melanin synthesis and reduced virulence[4][5][7]. The catalytic mechanism involves keto-enol tautomerization and syn elimination of water in an E1cb-like manner, with key residues (e.g., Asp-31, His-85) facilitating proton abstraction and stabilization of intermediates[3][9]. Structure-based inhibitor discovery exploiting the unique active site geometry has yielded potent synthetic fungicides[7].

Other names

scytalone 7,8-hydro-lyase, 1,3,8-trihydroxynaphthalene-formingSD

Competitive inhibition of the active site (for carpropamid and other inhibitors), Displacement of active-site water (for certain synthetic inhibitors), Inhibition of melanin pathway decreases fungal pathogenicity