Browsing by Author "Gergel, Sebastian"

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    Methylation of unactivated alkenes with engineered methyltransferases to generate non‐natural terpenoids
    (2023) Aberle, Benjamin; Kowalczyk, Daniel; Massini, Simon; Egler‐Kemmerer, Alexander‐N.; Gergel, Sebastian; Hammer, Stephan C.; Hauer, Bernhard
    Terpenoids are built from isoprene building blocks and have numerous biological functions. Selective late-stage modification of their carbon scaffold has the potential to optimize or transform their biological activities. However, the synthesis of terpenoids with a non-natural carbon scaffold is often a challenging endeavor because of the complexity of these molecules. Herein we report the identification and engineering of (S)-adenosyl-l-methionine-dependent sterol methyltransferases for selective C-methylation of linear terpenoids. The engineered enzyme catalyzes selective methylation of unactivated alkenes in mono-, sesqui- and diterpenoids to produce C11, C16 and C21 derivatives. Preparative conversion and product isolation reveals that this biocatalyst performs C-C bond formation with high chemo- and regioselectivity. The alkene methylation most likely proceeds via a carbocation intermediate and regioselective deprotonation. This method opens new avenues for modifying the carbon scaffold of alkenes in general and terpenoids in particular.