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Hedycaryol Synthase in Complex with Nerolidol Reveals Terpene Cyclase Mechanism
Author(s) -
Baer Philipp,
Rabe Patrick,
Citron Christian A.,
de Oliveira Mann Carina C.,
Kaufmann Norman,
Groll Michael,
Dickschat Jeroen S.
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300708
Subject(s) - carbocation , terpene , chemistry , nerolidol , stereochemistry , cyclase , ligand (biochemistry) , active site , atp synthase , enzyme , biochemistry , organic chemistry , receptor , chromatography , linalool , essential oil
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.