Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds

The growing number of immunocompromised patients begs for efficient therapy strategies against invasive fungal infections. As conventional antifungal treatment is increasingly hampered by resistance to commonly used antifungals, development of novel therapy regimens is required. On the other hand, numerous fungal species are industrially exploited as cell factories of enzymes and chemicals or as producers of medically relevant pharmaceuticals. Consequently, there is immense interest in tapping the almost inexhaustible fungal portfolio of natural products for potential medical and industrial applications. Both the pathogenicity and production of those small metabolites are significantly dependent on the acetylation status of distinct regulatory proteins. Thus, classical lysine deacetylases (KDACs) are crucial virulence determinants and important regulators of natural products of fungi. In this review, we present an overview of the members of classical KDACs and their complexes in filamentous fungi. Further, we discuss the impact of the genetic manipulation of KDACs on the pathogenicity and production of bioactive molecules. Special consideration is given to inhibitors of these enzymes and their role as potential new antifungals and emerging tools for the discovery of novel pharmaceutical drugs and antibiotics in fungal producer strains.

Automated summary

As the number of immunocompromised patients grows, there is a need for efficient therapy strategies against invasive fungal infections; conventional antifungal treatments are increasingly limited by drug resistance, necessitating the development of new therapies; there is immense potential in utilizing natural products from fungi for medical and industrial applications, with the acetylation status of regulatory proteins playing a significant role.