Hedycaryol Synthase in Complex with Nerolidol Reveals Terpene Cyclase Mechanism

ChemBioChem, 2014, DOI: 10.1002/cbic.201300708, Volume 15, Issue 2, pages 213–216 published on 24.01.2014

ChemBioChem, online article

The biosynthesis of terpenes is catalysed by class I and II terpene cyclases. Here we present structural data from a class I hedycaryol synthase in complex with nerolidol, serving as a surrogate for the reaction intermediate nerolidyl diphosphate. This prefolded ligand allows mapping of the active site and hence the identification of a key carbonyl oxygen of Val179, a highly conserved helix break (G1/2) and its corresponding helix dipole. Stabilising the carbocation at the substrate's C1 position, these elements act in concert to catalyse the 1,10 ring closure, thereby exclusively generating the anti-Markovnikov product. The delineation of a general mechanistic scaffold was confirmed by site-specific mutations. This work serves as a basis for understanding carbocation chemistry in enzymatic reactions and should contribute to future application of these enzymes in organic synthesis.  

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