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Related Experiment Video

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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028

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Host-Pathogen Interaction Activated Biosynthesis of Natural Products.

Yukiko Ujie¹, Shun Saito¹, Chisato Iwata¹

¹Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.

Journal of Natural Products

|August 28, 2025

Summary

Pathogenic fungi and immune cells interact, triggering the production of new survival compounds. This study reveals how host-pathogen interactions activate fungal genes, producing novel metabolites like fumigatinolactone.

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High Throughput Co-culture Assays for the Investigation of Microbial Interactions

High Throughput Co-culture Assays for the Investigation of Microbial Interactions

Published on: October 15, 2019

Area of Science:

Microbiology
Immunology
Natural Product Chemistry

Background:

Pathogenic microorganisms may produce survival compounds when attacked by immune cells.
Understanding host-pathogen interactions is crucial for developing new antimicrobial strategies.

Purpose of the Study:

To investigate the interaction between pathogenic fungi and immune cells.
To isolate and characterize novel natural products produced during this interaction.
To elucidate the mechanisms underlying the production of these compounds.

Main Methods:

Coculture of *Aspergillus fumigatus* with RAW264 mouse macrophage-like cells.
Isolation and structural elucidation of fumigatinolactone (1).
Investigation of the biosynthetic pathway and regulatory mechanisms.

Main Results:

Fumigatinolactone (1) was isolated as a new natural product.
Compound 1 is formed via nonenzymatic coupling of fumigatin (4) and fumarylazlactone (5).
Fungal response to nitric oxide (NO) induced fumigatin (4) production, while iron starvation induced fumarylazlactone (5) production.
Compounds 1-4 inhibited NO production by macrophages, suggesting a fungal defense mechanism.

Conclusions:

Host-pathogen survival interactions can activate silent fungal genes to produce novel secondary metabolites.
This study provides the first elucidation of interaction mechanisms between pathogen and immune cells leading to new compound production.
Findings suggest that manipulating host-pathogen interactions could be a strategy to discover new fungal metabolites.