Changing Face: A Key Residue for the Addition of Water by Sclareol Synthase.

Sclareol synthase from Salvia sclarea (SsSS) naturally acts on 8α-hydroxy-copalyl diphosphate ( 1 ), stereoselectively adding water to produce (13 R )-sclareol ( 2a ), and similarly yields hydroxylated products with manifold other such bicyclic diterpene precursors. Here a key residue for this addition of water was identified. Strikingly, substitution with glutamine switches stereochemical outcome with 1 , leading to selective production of (13 S )-sclareol ( 2b ). Moreover, changes to the stereospecificity of water addition with the structurally closely-related substrate copalyl diphosphate ( 4 ) could be accomplished with alternative substitutions. Thus, this approach is expected to provide biosynthetic access to both epimers of 13-hydroxylated derivatives of manifold labdane-related diterpenes.