title: Activation-independent cyclization of monoterpenoids.
abstract: The biosynthesis of cyclic monoterpenes (C(10)) generally requires the cyclization of an activated linear precursor (geranyldiphosphate) by specific terpene cyclases. Cyclic triterpenes (C(30)), on the other hand, originate from the linear precursor squalene by the action of squalene-hopene cyclases (SHCs) or oxidosqualene cyclases (OSCs). Here, we report a novel terpene cyclase from Zymomonas mobilis (ZMO1548-Shc) with the unique capability to cyclize citronellal to isopulegol. To our knowledge, ZMO1548-Shc is the first biocatalyst with diphosphate-independent monoterpenoid cyclase activity. A combinatorial approach using site-directed mutagenesis and modeling of the active site with a bound substrate revealed that the cyclization of citronellal proceeds via a different mechanism than that of the cyclization of squalene.
authors.affiliation: Institute of Microbiology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siedenburg
authors.forename: Dieter
authors.initials: D
authors.lastname: Jendrossek
authors.forename: Michael
authors.initials: M
authors.lastname: Breuer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Juhl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pleiss
authors.forename: Miriam
authors.initials: M
authors.lastname: Seitz
authors.forename: Janosch
authors.initials: J
authors.lastname: Klebensberger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hauer
mesh_terms: D000080462:Acyclic Monoterpenes; D000447:Aldehydes / Q000378:metabolism*; D020134:Catalytic Domain; D003500:Cyclization; D000081005:Cyclohexane Monoterpenes; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D039821:Monoterpenes / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D013729:Terpenes / Q000378:metabolism*; D017355:Zymomonas / Q000201:enzymology* / Q000378:metabolism*
chemical_list: D000080462:Acyclic Monoterpenes; D000447:Aldehydes; D000081005:Cyclohexane Monoterpenes; D004798:Enzymes; D039821:Monoterpenes; D013729:Terpenes; C409816:isopulegol; C108217:citronellal