Abstract
Fungi have the potential to produce various biologically active secondary metabolites. Fungal genomes contain far more genes for secondary metabolites than the number of metabolites that have been identified. In several studies, novel fungal metabolites were discovered on co-culturing fungus with another microorganism. Therefore, the coculturing method has attracted much attention in this field. However, study of the molecular mechanisms underlying this effect is in its infancy. In this research, we used strains of the fungal genus Aspergillus in co-culture to enhance secondary metabolites production. Aspergillus nidulans showed enhanced production of antibacterial compounds called diphenyl ethers when it was co-cultured with Aspergillus fumigatus. We identified a gene cluster (the ors cluster) that are involved in production of these metabolites. Notably, this cluster was previously demonstrated to be responsible for production of a different compound, orsellinic acid, when Aspergillus nidulans was co-cultured with the bacterium Streptomyces rapamycinicus. To gain insight into the differences in metabolite biosynthesis during fungal–bacterial and fungal–fungal interaction, the biosynthetic pathway of co-culture-induced metabolites were analyzed and reconstructed in Aspergillus oryzae. Our model co-culture system serves as a foundation for understanding fungal secondary metabolic response to fungal–fungal interaction.
