Structure and Function of a "Head‐to‐Middle" Prenyltransferase: Lavandulyl Diphosphate Synthase. (29th February 2016)

• Record Type: Journal Article
• Authors: Liu, Meixia; Chen, Chun‐Chi; Chen, Lu; Xiao, Xiansha; Zheng, Yingying; Huang, Jian‐Wen; Liu, Weidong; Ko, Tzu‐Ping; Cheng, Ya‐Shan; Feng, Xinxin; Oldfield, Eric; Guo, Rey‐Ting; Ma, Yanhe
• Is Part Of: Angewandte Chemie. Volume 128:Number 15(2016)
• Page Start: 4799
• Page End: 4802
• Publication Date: 2016-02-29
• Subjects: Biosynthese -- Duftstoffe -- Monoterpene -- Naturstoffe -- Strukturaufklärung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201600656
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Lavendelduft : Die Struktur der Lavandulyldiphosphat‐Synthase, einer irregulären Monoterpensynthase, wurde bestimmt. Sie ähnelt bemerkenswert den Strukturen der an der bakteriellen Zellwandbiosynthese beteiligten cis ‐Prenylsynthasen. Die Bestimmung zweier ligandengebundener Strukturen offenbarte einen ungewöhnlichen strukturbasierten Wirkmechanismus.