Immunosuppressive polyketides from mantis-associated Daldinia eschscholzii

Area of Science:

• Natural Product Chemistry
• Mycology
• Medicinal Chemistry

Background:

• Fungal polyketides are a rich source of bioactive compounds, including immunosuppressants.
• The fungus Daldinia eschscholzii is known to produce dalesconols A and B, but its full chemical diversity remains unexplored.
• Discovering novel polyketide architectures is crucial for identifying new drug and agrochemical leads.

Purpose of the Study:

• To investigate the chemical diversity of polyketides produced by the mantis-associated fungus Daldinia eschscholzii.
• To elucidate the biosynthetic pathways of novel fungal polyketides.
• To identify and characterize new immunosuppressive compounds for potential therapeutic applications.

Main Methods:

• Scaled-up fermentation of Daldinia eschscholzii.
• Isolation and structural characterization of polyketide metabolites using spectroscopic techniques.
• Analysis of intermediate metabolites to infer biosynthetic pathways.
• Evaluation of immunosuppressive activity of isolated compounds.

Main Results:

• Simultaneous generation of four novel polyketide skeletons by Daldinia eschscholzii.
• Identification of seven structurally unique and substantially immunosuppressive compounds.
• Elucidation of four distinct polyketide biosynthetic pathways, initiated by varying acetate unit condensations.
• First-time description of a decarbonylation reaction in triketone metabolism and structural correction of known compounds (sporothrin C, nodulone).

Conclusions:

• Daldinia eschscholzii produces a diverse array of novel immunosuppressive polyketides with unique chemical architectures.
• The study provides insights into fungal polyketide biosynthesis and identifies promising candidates for drug discovery.
• The identified compounds and biosynthetic pathways represent significant advancements in natural product chemistry and medicinal chemistry.