title: Onocerin Biosynthesis Requires Two Highly Dedicated Triterpene Cyclases in a Fern Lycopodium clavatum.
abstract: Onocerin is known for its unusual structure among triterpenoids, with a symmetrical structure that is formed by cyclizations at the both termini of dioxidosqualene. The nature of the enzyme catalyzing these unusual cyclizations has remained elusive for decades. Here, we report the cloning of genes responsible for these reactions; they exhibited unprecedented substrate specificities among oxidosqualene cyclase family members. Two genes, LCC and LCD, were identified from the fern Lycopodium clavatum. Expression in yeast revealed that both were required to produce α-onocerin. LCC, the first dioxidosqualene cyclase, catalyzed the production of a novel intermediate pre-α-onocerin from only dioxidosqualene as a substrate; LCD catalyzed the second half of the cyclization, exclusively from pre-α-onocerin. These results demonstrated that these two most unusual oxidosqualene cyclases were involved in onocerin biosynthesis.
authors.affiliation: Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Araki
authors.affiliation: Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Saga
authors.affiliation: Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
authors.forename: Momo
authors.initials: M
authors.lastname: Marugami
authors.affiliation: Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
authors.forename: Junnosuke
authors.initials: J
authors.lastname: Otaka
authors.affiliation: Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Araya
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8675, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Saito
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8675, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba, 292-0818, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan. kushiro@meiji.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kushiro
mesh_terms: D053898:Biosynthetic Pathways; D003500:Cyclization; D017343:Genes, Plant; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism*; D032502:Lycopodium / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014315:Triterpenes; C409888:alpha-onocerin; D019751:Intramolecular Transferases; C021924:lanosterol synthase
keywords: biosynthesis; dioxidosqualene; onocerin; terpene cyclization; terpenoids