From the forest floor to the lab: Insights into the diversity and complexity of mushroom polyketide synthases

Abstract

Mushroom-forming fungi exhibit a distinctive ecology, which is unsurprisingly also reflected in unique and divergent biosynthetic pathways. We review this phenomenon through the lens of the polyketide metabolism, where mushrooms often deviate from established principles and challenge conventional paradigms. This is evident not only by non-canonical enzyme architectures and functions but also by their propensity for multi-product synthases rather than single-product pathways. Nevertheless, mushrooms also feature many polyketides familiar from plants, bacteria, and fungi of their sister division Ascomycota, which, however, are the result of an independent evolution. In this regard, the captivating biosynthetic pathways of mushrooms might even help us understand the biological pressures that led to the simultaneous production of the same natural products (via convergent evolution, co-evolution, and/or metaevolution) and thus address the question of their raison d'être.