A Branched Diterpene Cascade: The Mechanism of Spinodiene Synthase from Saccharopolyspora spinosa.

A diterpene synthase from Saccharopolyspora spinosa was found to convert geranylgeranyl diphosphate into the new natural products spinodiene A and B, accompanied by 2,7,18-dolabellatriene. The structures and the formation mechanism of the enzyme products were investigated by extensive isotopic labelling experiments, revealing an unusual branched isomerisation mechanism towards the neutral intermediate 2,7,18-dolabellatriene. A Diels-Alder approach was used to convert the main diterpene product with its rare conjugated diene moiety into formal sesterterpene alcohols.