Regulation of azalomycin F production in Streptomyces iranensis required for activation of fungal silent gene clusters

Streptomycetes are renowned producers of secondary metabolites, which are compounds that are not directly required for the survival of the producing organism but rather provide an advantage under certain ecological conditions. Thus, the biosynthetic gene clusters (BGCs) encoding the machinery to produce these compounds are often only active when these specific conditions are met. As we have previously shown, Streptomyces iranensis HM35 (DSM 41954) has the ability to activate the production of orsellinic acid and various derivatives thereof in the fungus Aspergillus nidulans 1,2. Furthermore, we were able to show that S. iranensis can activate silent BGCs in various fungi through the secondary metabolite azalomycin F33. To gain a better understanding of this microbial interaction, we further investigated the genetic regulation of azalomycin F production. By conducting deletion experiments, we identified a group of major regulatory genes located in a regulatory island. It encodes four LuxR-type transcription factors and is required for the interaction between S. iranensis and A. nidulans. Furthermore, we were able to verify that the encoded regulators are involved in the production of azalomycin F3, which mediates the interaction of S. iranensis and A. nidulans. Through transcriptomic analysis and protein-DNA interaction studies we aim to identify the target genes and exact binding motifs of the regulators as well as their potential involvement in mechanisms of export or transport of azalomycin F3 to the recipient fungus. Our data provide insight into the molecular regulation of bacterial-fungal interactions and the complex network of transcription factors involved.

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