Loading [MathJax]/extensions/MathMenu.js

Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Henry Struwe
  • Trang Nguyen
  • Svenja Schwörer
  • Jörn Droste
  • Hanke Spinck
  • Andreas Kirschning

Research Organisations

External Research Organisations

  • Uppsala University

Details

Original languageEnglish
Pages (from-to)498–508
Number of pages11
JournalBiochemistry
Volume64
Issue number2
Early online date28 Dec 2024
Publication statusPublished - 2025

Abstract

Farnesyl pyrophosphate derivatives bearing an additional oxygen atom at position 5 proved to be very suitable for expanding the substrate promiscuity of sesquiterpene synthases (STSs) and the formation of new oxygenated terpenoids. Insertion of an oxygen atom in position 9, however, caused larger restraints that led to restricted acceptance by STSs. In order to reduce some of the proposed restrictions, two FPP-ether derivatives with altered substitution pattern around the terminal olefinic double bond were designed. These showed improved promiscuity toward different STSs. Four new cyclized terpenoids with an embedded ether group were isolated and characterized. In the case of two cyclic enol ethers, also the corresponding “hydrolysis” products, linear hydroxyaldehydes, were isolated. Interestingly, all cyclization products originate from an initial 1 → 12 cyclization unprecedented when native farnesyl pyrophosphate serves as a substrate. We found that the most suitable FPP derivative with an additional oxygen at position 9 does not carry any methyl group on the terminal alkene, which likely reduces steric congestion when the preferred conformation for cyclization is adopted in the active site.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives. / Struwe, Henry; Nguyen, Trang; Schwörer, Svenja et al.
In: Biochemistry, Vol. 64, No. 2, 2025, p. 498–508.

Research output: Contribution to journalArticleResearchpeer review

Struwe H, Nguyen T, Schwörer S, Droste J, Spinck H, Kirschning A. Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives. Biochemistry. 2025;64(2):498–508. Epub 2024 Dec 28. doi: 10.1021/acs.biochem.4c00589
Struwe, Henry ; Nguyen, Trang ; Schwörer, Svenja et al. / Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives. In: Biochemistry. 2025 ; Vol. 64, No. 2. pp. 498–508.
Download
@article{d89e24398cc0423f801c2616735f1063,
title = "Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives",
abstract = "Farnesyl pyrophosphate derivatives bearing an additional oxygen atom at position 5 proved to be very suitable for expanding the substrate promiscuity of sesquiterpene synthases (STSs) and the formation of new oxygenated terpenoids. Insertion of an oxygen atom in position 9, however, caused larger restraints that led to restricted acceptance by STSs. In order to reduce some of the proposed restrictions, two FPP-ether derivatives with altered substitution pattern around the terminal olefinic double bond were designed. These showed improved promiscuity toward different STSs. Four new cyclized terpenoids with an embedded ether group were isolated and characterized. In the case of two cyclic enol ethers, also the corresponding “hydrolysis” products, linear hydroxyaldehydes, were isolated. Interestingly, all cyclization products originate from an initial 1 → 12 cyclization unprecedented when native farnesyl pyrophosphate serves as a substrate. We found that the most suitable FPP derivative with an additional oxygen at position 9 does not carry any methyl group on the terminal alkene, which likely reduces steric congestion when the preferred conformation for cyclization is adopted in the active site.",
author = "Henry Struwe and Trang Nguyen and Svenja Schw{\"o}rer and J{\"o}rn Droste and Hanke Spinck and Andreas Kirschning",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Published by American Chemical Society.",
year = "2025",
doi = "10.1021/acs.biochem.4c00589",
language = "English",
volume = "64",
pages = "498–508",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "2",

}

Download

TY - JOUR

T1 - Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives

AU - Struwe, Henry

AU - Nguyen, Trang

AU - Schwörer, Svenja

AU - Droste, Jörn

AU - Spinck, Hanke

AU - Kirschning, Andreas

N1 - Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.

PY - 2025

Y1 - 2025

N2 - Farnesyl pyrophosphate derivatives bearing an additional oxygen atom at position 5 proved to be very suitable for expanding the substrate promiscuity of sesquiterpene synthases (STSs) and the formation of new oxygenated terpenoids. Insertion of an oxygen atom in position 9, however, caused larger restraints that led to restricted acceptance by STSs. In order to reduce some of the proposed restrictions, two FPP-ether derivatives with altered substitution pattern around the terminal olefinic double bond were designed. These showed improved promiscuity toward different STSs. Four new cyclized terpenoids with an embedded ether group were isolated and characterized. In the case of two cyclic enol ethers, also the corresponding “hydrolysis” products, linear hydroxyaldehydes, were isolated. Interestingly, all cyclization products originate from an initial 1 → 12 cyclization unprecedented when native farnesyl pyrophosphate serves as a substrate. We found that the most suitable FPP derivative with an additional oxygen at position 9 does not carry any methyl group on the terminal alkene, which likely reduces steric congestion when the preferred conformation for cyclization is adopted in the active site.

AB - Farnesyl pyrophosphate derivatives bearing an additional oxygen atom at position 5 proved to be very suitable for expanding the substrate promiscuity of sesquiterpene synthases (STSs) and the formation of new oxygenated terpenoids. Insertion of an oxygen atom in position 9, however, caused larger restraints that led to restricted acceptance by STSs. In order to reduce some of the proposed restrictions, two FPP-ether derivatives with altered substitution pattern around the terminal olefinic double bond were designed. These showed improved promiscuity toward different STSs. Four new cyclized terpenoids with an embedded ether group were isolated and characterized. In the case of two cyclic enol ethers, also the corresponding “hydrolysis” products, linear hydroxyaldehydes, were isolated. Interestingly, all cyclization products originate from an initial 1 → 12 cyclization unprecedented when native farnesyl pyrophosphate serves as a substrate. We found that the most suitable FPP derivative with an additional oxygen at position 9 does not carry any methyl group on the terminal alkene, which likely reduces steric congestion when the preferred conformation for cyclization is adopted in the active site.

UR - http://www.scopus.com/inward/record.url?scp=85213415249&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.4c00589

DO - 10.1021/acs.biochem.4c00589

M3 - Article

AN - SCOPUS:85213415249

VL - 64

SP - 498

EP - 508

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 2

ER -

By the same author(s)