Traversing the fungal terpenome

Area of Science:

• Fungal natural product biosynthesis
• Metabolic engineering
• Bioinformatics

Background:

• Fungi, particularly Ascomycota and Basidiomycota, synthesize a wide array of terpenoid compounds.
• While terpenoid biosynthesis is understood in Ascomycota, pathways in Basidiomycota remain largely uncharacterized.
• Basidiomycota produce diverse sesquiterpenoids, including trans-humulyl cation derived compounds with significant bioactivity.

Purpose of the Study:

• To explore the potential of fungal terpenoid biosynthesis for discovering new natural products.
• To investigate the application of genome sequencing and bioinformatics for identifying fungal terpenoid biosynthetic gene clusters.
• To highlight the utility of heterologous pathway refactoring for producing pharmaceutically relevant fungal terpenoids.

Main Methods:

• Genome sequencing and mining to identify biosynthetic gene clusters.
• Bioinformatic analysis to predict gene functions and pathways.
• Heterologous expression and refactoring of biosynthetic pathways in a model host.

Main Results:

• Identification of biosynthetic gene clusters for fungal terpenoids, including those derived from trans-humulyl cation.
• Demonstration of the feasibility of using genome mining to discover novel terpenoid pathways.
• Potential for heterologous production of complex fungal terpenoids.

Conclusions:

• Genome mining and bioinformatics are powerful tools for uncovering fungal terpenoid biosynthetic pathways.
• Heterologous pathway refactoring offers a viable strategy for the production of pharmaceutically important fungal terpenoids.
• Further research into Basidiomycota terpenoids promises significant discoveries for drug development.