An Unusual Skeletal Rearrangement in the Biosynthesis of the Sesquiterpene Trichobrasilenol from Trichoderma. Issue 42 (9th September 2019)

• Record Type: Journal Article
• Authors: Murai, Keiichi; Lauterbach, Lukas; Teramoto, Kazuya; Quan, Zhiyang; Barra, Lena; Yamamoto, Tsuyoshi; Nonaka, Kenichi; Shiomi, Kazuro; Nishiyama, Makoto; Kuzuyama, Tomohisa; Dickschat, Jeroen S.
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 42(2019)
• Page Start: 15046
• Page End: 15050
• Publication Date: 2019-09-09
• Subjects: biosynthesis -- enzyme mechanisms -- isotopes -- NMR spectroscopy -- terpenes; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201907964
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The skeletons of some classes of terpenoids are unusual in that they contain a larger number of Me groups (or their biosynthetic equivalents such as olefinic methylene groups, hydroxymethyl groups, aldehydes, or carboxylic acids and their derivatives) than provided by their oligoprenyl diphosphate precursor. This is sometimes the result of an oxidative ring‐opening reaction at a terpene‐cyclase‐derived molecule containing the regular number of Me group equivalents, as observed for picrotoxan sesquiterpenes. In this study a sesquiterpene cyclase from Trichoderma spp. is described that can convert farnesyl diphosphate (FPP) directly via a remarkable skeletal rearrangement into trichobrasilenol, a new brasilane sesquiterpene with one additional Me group equivalent compared to FPP. A mechanistic hypothesis for the formation of the brasilane skeleton is supported by extensive isotopic labelling studies. Abstract : Out of the ordinary : Trichobrasilenol was identified as an unusual sesquiterpene alcohol made by a sesquiterpene cyclase from Trichoderma spp. The mechanism of product formation was studied by using isotopically labelled substrates, with a special emphasis on a complex rearrangement step that leads to the extrusion of a hydroxymethyl group from an internal methylene group of FPP.