Publikation:

Non‐canonical C16 Homoterpene Biosynthesis Widespread in Actinobacteria

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2025

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Deutsche Forschungsgemeinschaft (DFG): 513519240
Deutsche Forschungsgemeinschaft (DFG): 510974120

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Angewandte Chemie International Edition. Wiley. 2025, 64(5), e202418613. ISSN 1433-7851. eISSN 1521-3773. Verfügbar unter: doi: 10.1002/anie.202418613

Zusammenfassung

A novel biosynthetic pathway towards the rare and underexplored non‐canonical family of homoterpenes was discovered in actinobacteria through targeted genome mining and enzymatic in vitro reconstitution. The pathway comprises initial methylation‐induced double bond isomerization of farnesyl diphosphate (FPP) to (2E,7E)‐6‐methyl‐farnesyl diphosphate, catalyzed by a novel family of methyltransferases with unique dual function. The resulting linear C16 double bond isomer of FPP constitutes the specific substrate for a distinct family of type I terpene cyclases, catalyzing diverse cyclization reactions. Functional characterization of nine enzyme pairs led to discovery of five unprecedented homoterpene natural products. The enzymological novelty enable the development of novel biocatalytic and genetically programmable synthetic strategies towards methylated terpenoids with potentially unique properties (“magic methyl effect”).

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540 Chemie

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actinobacteria, biosynthesis, enzyme discovery, non-canonical terpenoids, terpenoids

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ISO 690REUTER, Tatjana, Lars DIEMINGER, Sarah STEIDLE, Katrin ZOLLER, Maximilian HOLOCHER, Lin ZHOU, Dominik HANAUSKA, Katharina RACZ, Lena BARRA, 2025. Non‐canonical C16 Homoterpene Biosynthesis Widespread in Actinobacteria. In: Angewandte Chemie International Edition. Wiley. 2025, 64(5), e202418613. ISSN 1433-7851. eISSN 1521-3773. Verfügbar unter: doi: 10.1002/anie.202418613
BibTex
@article{Reuter2025-01-27Nonca-71591,
  title={Non‐canonical C16 Homoterpene Biosynthesis Widespread in Actinobacteria},
  year={2025},
  doi={10.1002/anie.202418613},
  number={5},
  volume={64},
  issn={1433-7851},
  journal={Angewandte Chemie International Edition},
  author={Reuter, Tatjana and Dieminger, Lars and Steidle, Sarah and Zoller, Katrin and Holocher, Maximilian and Zhou, Lin and Hanauska, Dominik and Racz, Katharina and Barra, Lena},
  note={Article Number: e202418613}
}
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