Terpene synthases catalyse the conversion of acyclic and achiral oligoprenyl diphosphate precursors into usually (poly)cyclic, chiral and enantiomerically enriched terpene hydrocarbons or alcohols. These reactions proceed with multiple carbon-carbon bond formations and changes of the hybridisation of often more than half of the precursor carbons in just one enzymatic step. The mechanisms of terpene synthases can be investigated through isotopic labelling experiments,[1,2] structure based site-directed mutagenesis,[4,5] computational chemistry, and, ideally, combinations thereof. Enzyme variants obtained through site-directed mutagenesis often show the formation of new products, making this approach interesting to expand the reachable chemical space. Further possibilities include the usage of terpene synthases for the conversion of non-natural substrate analogs. This approach demonstrates a remarkable tolerance of terpene synthases towards substrate modifications and allows for the efficient enzymatic synthesis of highly complex non-natural terpene analogs.
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