Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus Calidoustus

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2022 Jan 24

PMID 35072966

Authors

Zhiyang Quan

Anwei Hou

Bernd Goldfuss

Jeroen S Dickschat

Affiliations

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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.

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