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

被引：70

作者：

Quan, Zhiyang ^{[1
]}

Hou, Anwei ^{[1
]}

Goldfuss, Bernd ^{[2
]}

Dickschat, Jeroen S. ^{[1
]}

机构：

[1] Univ Bonn, Inst Organ Chem & Biochem, Gerhard Domagk Str 1, D-53121 Bonn, Germany

[2] Univ Cologne, Dept Chem, Greinstr 4, D-50939 Cologne, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 13期

关键词：

DFT Calculations; Enzyme Mechanisms; Isotopes; Substrate Analogues; Terpenoids; GENOME MINING APPROACH; OPHIOBOLIN F SYNTHASE; TERPENE SYNTHASES; BIOSYNTHESIS; DISCOVERY; REVEALS;

D O I：

10.1002/anie.202117273

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：7

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