Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from <i>Aspergillus calidoustus</i>
Zhiyang Quan, Anwei Hou, Bernd Goldfuß, Jeroen S. Dickschat
Abstract
The multiproduct chimeric sesterterpene synthase AcAS from Aspergillus calidoustus yielded spirocyclic calidoustene, which exhibits a novel skeleton, besides five known sesterterpenes. The complex cyclisation mechanism to all six compounds was investigated by isotopic labelling experiments in combination with DFT calculations. Chemically synthesised 8-hydroxyfarnesyl diphosphate was converted with isopentenyl diphosphate and AcAS into four oxygenated sesterterpenoids that structurally resemble cytochrome P450 oxidation products of the sesterterpene hydrocarbons. Protein engineering of AcAS broadened the substrate scope and gave significantly improved enzyme yields.
Topics & Concepts
BifunctionalATP synthaseAspergillusMechanism (biology)Product (mathematics)ChemistryStereochemistryMicrobiologyBiologyBiochemistryEnzymeMathematicsPhilosophyCatalysisEpistemologyGeometryPlant biochemistry and biosynthesisMicrobial Natural Products and BiosynthesisMicrobial Metabolism and Applications