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  • 1Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78464, Konstanz, Germany.

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|November 17, 2025
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Summary
This summary is machine-generated.

Scientists discovered the first fungal homoterpene pathway, challenging the isoprene rule. This finding reveals novel natural products and evolutionary insights into terpene biosynthesis.

Keywords:
Apple cankerEnzyme discoveryHomoterpenesIsoprene ruleNon‐canonical terpenoids

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Area of Science:

  • Natural Product Chemistry
  • Biochemistry
  • Mycology

Background:

  • Homoterpenes, natural products with methylated backbones, challenge the traditional isoprene rule.
  • Biosynthetic pathways for homoterpenes are known in bacteria but not previously in fungi.
  • The biogenic isoprene rule posits terpenes are composed of C5 units.

Purpose of the Study:

  • To discover the first homoterpene biosynthetic pathway in the fungal kingdom.
  • To investigate the enzymes involved in fungal homoterpene production.
  • To understand the evolutionary origins of fungal homoterpene biosynthesis.

Main Methods:

  • Targeted genomic data mining in fungi.
  • In vitro reconstitution of identified biosynthetic pathways.
  • Functional analysis of methyltransferase (NdiMT) and terpene cyclase (NdiTC) enzymes.
  • Phylogenetic analyses of gene origins.

Main Results:

  • Discovery of the first fungal homoterpene biosynthetic pathway in *Neonectria ditissima*.
  • Identification of a novel homosesquiterpene with a heptamethylbicyclo[3.3.1]nonane scaffold.
  • Evidence of horizontal gene transfer of a methyltransferase from bacteria to the fungus.
  • Indication that the terpene cyclase evolved from a fungal ancestor.

Conclusions:

  • Fungi possess pathways for producing homoterpenes, expanding their known biosynthetic capabilities.
  • The discovery of a novel methylated terpene scaffold provides new chemical diversity.
  • Horizontal gene transfer plays a role in the evolution of novel natural product pathways in fungi.
  • The findings prompt further research into the evolutionary and functional significance of terpene methylation.