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

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 combin...

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Autores principales: Quan, Zhiyang, Hou, Anwei, Goldfuss, Bernd, Dickschat, Jeroen S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303889/
https://www.ncbi.nlm.nih.gov/pubmed/35072966
http://dx.doi.org/10.1002/anie.202117273
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author Quan, Zhiyang
Hou, Anwei
Goldfuss, Bernd
Dickschat, Jeroen S.
author_facet Quan, Zhiyang
Hou, Anwei
Goldfuss, Bernd
Dickschat, Jeroen S.
author_sort Quan, Zhiyang
collection PubMed
description 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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spelling pubmed-93038892022-07-28 Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus Quan, Zhiyang Hou, Anwei Goldfuss, Bernd Dickschat, Jeroen S. Angew Chem Int Ed Engl Research Articles 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. John Wiley and Sons Inc. 2022-02-04 2022-03-21 /pmc/articles/PMC9303889/ /pubmed/35072966 http://dx.doi.org/10.1002/anie.202117273 Text en © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Quan, Zhiyang
Hou, Anwei
Goldfuss, Bernd
Dickschat, Jeroen S.
Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus
title Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus
title_full Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus
title_fullStr Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus
title_full_unstemmed Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus
title_short Mechanism of the Bifunctional Multiple Product Sesterterpene Synthase AcAS from Aspergillus calidoustus
title_sort mechanism of the bifunctional multiple product sesterterpene synthase acas from aspergillus calidoustus
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303889/
https://www.ncbi.nlm.nih.gov/pubmed/35072966
http://dx.doi.org/10.1002/anie.202117273
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