title: Cyclization of squalene from both termini: identification of an onoceroid synthase and enzymatic synthesis of ambrein.
abstract: The onoceroids are triterpenoids biosynthesized from squalene or (3S)-2,3-oxidosqualene by cyclization from both termini. We recently revealed that tetraprenyl-β-curcumene cyclase from Bacillus megaterium (BmeTC) is a bifunctional triterpene/sesquarterpene cyclase that converts head-to-tail tetraprenyl-β-curcumene and tail-to-tail squalene into pentacyclic and bicyclic products, respectively, in vivo. Here, we reveal that BmeTC has an unprecedented catalytic function in cyclizing squalene from both termini and is the first onoceroid synthase. We also report the first onoceroids from bacterial origin. Our discoveries suggest that symmetric and asymmetric onoceroids could be biosynthesized by a single enzyme via an intermediate cyclized at one terminus of squalene. Furthermore, the new function of BmeTC enabled the synthesis of (+)-ambrein, a major constituent of ambergris that is difficult to obtain naturally, via a mutated squalene-hopene cyclase-catalyzed reaction from easily available squalene.
authors.affiliation: Department of Applied Biological Chemistry and Graduate School of Science and Technology, Niigata University , Ikarashi 2-8050, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Ueda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hoshino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
mesh_terms: D003500:Cyclization; D008401:Gas Chromatography-Mass Spectrometry; D008025:Ligases / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009284:Naphthols / Q000138:chemical synthesis*; D013185:Squalene / Q000737:chemistry*; D014315:Triterpenes / Q000138:chemical synthesis
chemical_list: D009284:Naphthols; D014315:Triterpenes; C074170:ambrein; D013185:Squalene; D008025:Ligases