title: Structure and Function of a "Head-to-Middle" Prenyltransferase: Lavandulyl Diphosphate Synthase.
abstract: We report the first X-ray structure of the unique "head-to-middle" monoterpene synthase, lavandulyl diphosphate synthase (LPPS). LPPS catalyzes the condensation of two molecules of dimethylallyl diphosphate (DMAPP) to form lavandulyl diphosphate, a precursor to the fragrance lavandulol. The structure is similar to that of the bacterial cis-prenyl synthase, undecaprenyl diphosphate synthase (UPPS), and contains an allylic site (S1) in which DMAPP ionizes and a second site (S2) which houses the DMAPP nucleophile. Both S-thiolo-dimethylallyl diphosphate and S-thiolo-isopentenyl diphosphate bind intact to S2, but are cleaved to (thio)diphosphate, in S1. His78 (Asn in UPPS) is essential for catalysis and is proposed to facilitate diphosphate release in S1, while the P1 phosphate in S2 abstracts a proton from the lavandulyl carbocation to form the LPP product. The results are of interest since they provide the first structure and structure-based mechanism of this unusual prenyl synthase.
authors.affiliation: College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Liu
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL, 61801, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Xiansha
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: AsiaPac Biotechnology Co., Ltd., Dongguan, 523808, China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Huang
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Tzu-Ping
authors.initials: TP
authors.lastname: Ko
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Ya-Shan
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA. eo@chad.scs.uiuc.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Oldfield
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. guo_rt@tib.cas.cn.
authors.forename: Rey-Ting
authors.initials: RT
authors.lastname: Guo
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. ma_yh@tib.cas.cn.
authors.forename: Yanhe
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000080462:Acyclic Monoterpenes; D018360:Crystallography, X-Ray; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D039821:Monoterpenes / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D004122:Dimethylallyltranstransferase; C492921:lavandulol
keywords: biosynthesis; fragrance; monoterpenes; natural products; structure elucidation