473-03-0Relevant articles and documents
Cyclization of squalene from both termini: Identification of an onoceroid synthase and enzymatic synthesis of ambrein
Ueda, Daijiro,Hoshino, Tsutomu,Sato, Tsutomu
, p. 18335 - 18338 (2013)
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.
Analysis of the Catalytic Mechanism of Bifunctional Triterpene/Sesquarterpene Cyclase: Tyr167 Functions To Terminate Cyclization of Squalene at the Bicyclic Step
Tenkovskaia, Liudmila,Murakami, Mizuki,Okuno, Kotone,Ueda, Daijiro,Sato, Tsutomu
, p. 1910 - 1913 (2017/09/28)
Onoceroids are a group of triterpenes biosynthesized from squalene or dioxidosqualene by cyclization from both termini. We previously identified a bifunctional triterpene/sesquarterpene cyclase (TC) that constructs a tetracyclic scaffold from tetraprenyl-β-curcumene (C35) but a bicyclic scaffold from squalene (C30) in the first reaction. TC also accepts the bicyclic intermediate as a substrate and generates tetracyclic and pentacyclic onoceroids in the second reaction. In this study, we analyzed the catalytic mechanism of an onoceroid synthase by using mutated enzymes. TCY167A produced an unnatural tricyclic triterpenol, but TCY167L, TCY167F, and TCY167W formed small quantities of tricyclic compounds, which suggested that the bulk size at Y167 contributed to termination of the cyclization of squalene at the bicyclic step. Our findings provide insight into the unique catalytic mechanism of TC, which triggers different cyclization modes depending on the substrate. These findings may facilitate the large-scale production of an onoceroid for which natural sources are limited.
METHOD FOR PRODUCING AMBREIN
-
Paragraph 0101; 0107-0109, (2016/08/23)
Provided is a method for producing ambrein, comprising reacting tetraprenyl-β-curcumene cyclase with 3-deoxyachilleol A to obtain ambrein.
Synthesis of (+)-Ambrein
Tanimoto, Hisahide,Oritani, Takayuki
, p. 3527 - 3536 (2007/10/03)
Enantiomerically pure (+)-Ambrein was synthesized from (+)-drimane-8,11-diol prepared via lipase catalyzed kinetic resolution, and easily prepared (i)-γ-cyclogeraniol.
Triterpenoid Total Synthesis, I: Synthesis of Ambrein and Ambrox
Mori, Kenji,Tamura, Hiroshi
, p. 361 - 368 (2007/10/02)
The first total synthesis of (+)-ambrein (1), a triterpene alcohol isolated from ambergris, was achieved.Both the enantiomers of ambrox (2) were also synthesized.
