Structure and Mechanism of the Monoterpene Cyclolavandulyl Diphosphate Synthase that Catalyzes Consecutive Condensation and Cyclization

We report the three‐dimensional structure of cyclolavandulyl diphosphate (CLPP) synthase (CLDS), which consecutively catalyzes the condensation of two molecules of dimethylallyl diphosphate (DMAPP) followed by cyclization to form a cyclic monoterpene, CLPP. The structures of apo‐CLDS and CLDS in com...

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Bibliographic Details
Published inAngewandte Chemie Vol. 129; no. 47; pp. 15109 - 15113
Main Authors Tomita, Takeo, Kobayashi, Masaya, Karita, Yuma, Yasuno, Yoko, Shinada, Tetsuro, Nishiyama, Makoto, Kuzuyama, Tomohisa
Format Journal Article
LanguageEnglish
German
Published Weinheim Wiley Subscription Services, Inc 20.11.2017
Subjects
Biosynthese
Chemical reactions
Chemistry
Condensation
Cyclisierung
Kopf-zu-Mitte-Kondensation
Kristallstrukturen
Magnesium
Mutagenesis
Terpen-Synthasen
Terpene synthase
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Summary:We report the three‐dimensional structure of cyclolavandulyl diphosphate (CLPP) synthase (CLDS), which consecutively catalyzes the condensation of two molecules of dimethylallyl diphosphate (DMAPP) followed by cyclization to form a cyclic monoterpene, CLPP. The structures of apo‐CLDS and CLDS in complex with Tris, pyrophosphate, and Mg2+ ion were refined at 2.00 Å resolution and 1.73 Å resolution, respectively. CLDS adopts a typical fold for cis‐prenyl synthases and forms a homo‐dimeric structure. An in vitro reaction using a regiospecifically 2H‐substituted DMAPP substrate revealed the intramolecular proton transfer mechanism of the CLDS reaction. The CLDS structure and structure‐based mutagenesis provide mechanistic insights into this unprecedented terpene synthase. The combination of structural and mechanistic insights advances the knowledge of intricate terpene synthase‐catalyzed reactions. Eine Synthase, die beides kann: Cyclolavandulyldiphosphat(CLPP)‐Synthase (CLDS) katalysiert die „Kopf‐zu‐Mitte”‐Kondensation von zwei Molekülen Dimethylallyldiphosphat (DMAPP) und die anschließende Cyclisierung zu CLPP. Die Kristallstruktur von CLDS im Komplex mit Tris, Pyrophosphat und Mg2+ wurde mit 1.73 Å Auflösung bestimmt. Eine In‐vitro‐Reaktion mit regiospezifisch deuteriertem DMAPP, die CLDS‐Struktur und Mutagenese liefern Einblicke in den Mechanismus dieser einzigartigen Terpensynthase.
Bibliography:These authors contributed equally to this work.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201708474