Abstract
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.
Highlights
The physiologically diverse fungal kingdom plays an indispensable ecological role in the recycling of organic material and as symbionts of bacteria, plants, and animals on land or in aqueous habitats
Because trichostatin A (TSA) inhibits classical Keywords: lysine deacetylase (KDAC) activity, these results suggest that the acetylation status of histones and/or other regulatory factors have a significant impact on secondary metabolites (SMs) production
This study revealed that NaB, valproic acid (VPA), and TSA have a strong impact on SM biosynthesis in a media, time, and target-dependent way
Summary
The physiologically diverse fungal kingdom plays an indispensable ecological role in the recycling of organic material and as symbionts of bacteria, plants, and animals on land or in aqueous habitats. Others are acting as parasites or dreaded pathogens of plants and animals [2,3,4,5] In humans, they are responsible for superficial, invasive, and systemic infections. Considering the poor prognosis for patients suffering from systemic infections in advanced stages and the fact that available drugs might have severe side effects, development of novel and more efficient therapies is a matter of urgency [12,13]. This is even more important as fungal pathogens are increasingly developing resistances to conventional therapeutics [14,15]. The impact of classical KDACs for fungal SM production is another subject of this review
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