Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives.

Farnesyl pyrophosphate derivatives bearing an additional oxygen atom at position 5 proved to be very suitable for expanding the substrate promiscuity of sesquiterpene synthases (STSs) and the formation of new oxygenated terpenoids. Insertion of an oxygen atom in position 9, however, caused larger restraints that led to restricted acceptance by STSs. In order to reduce some of the proposed restrictions, two FPP-ether derivatives with altered substitution pattern around the terminal olefinic double bond were designed.

Sesquiterpene Backbones Generated by Sesquiterpene Cyclases: Formation of -Caryolan-1-ol and an Isoclovane.

New sesquiterpene backbones are accessible after incubation of caryolan-synthase (GcoA) and presilphiperfolan-8-β-ol synthase (BcBOT2) with a non-natural farnesyldiphosphate in which the central olefinic double bond is isomerized toward the methyl group. Two newly formed sesquiterpenoids are reported, a constitutional isomer of caryolan-1-ol (), which we name -caryolan-1-ol (), and the first terpenoid based on the isoclovane ring skeleton generated enzymatically thus far.