Fungal UDP-glycosyltransferase (UGT)

Fungal UDP-glycosyltransferases (UGTs) are enzymes that facilitate the transfer of sugar residues from nucleotide-activated donor molecules to a wide array of acceptors, including sterols, proteins, and secondary metabolites [1]. These enzymes are pivotal for the structural integrity of the fungal cell wall and the regulation of membrane fluidity through the synthesis of steryl glycosides [2]. In pathogenic species like Candida albicans and Aspergillus fumigatus, UGTs contribute to virulence and the ability to withstand environmental stress, including the presence of antifungal agents [3]. By glycosylating and thereby neutralizing toxic compounds, UGTs also serve as a mechanism for antifungal resistance [4]. While they represent a promising target for novel antifungal development, the high degree of structural similarity between certain fungal UGTs and human UDP-glucuronosyltransferases poses a significant challenge for drug selectivity [5]. Current therapeutic strategies aim to identify fungal-specific motifs to minimize off-target effects on human drug metabolism [6]. Inhibition of these enzymes can lead to compromised cell wall stability and increased susceptibility to existing antifungal treatments [3]. Research is ongoing to develop small-molecule inhibitors that can specifically bind the fungal enzyme's active site without affecting host physiology [6].

Other names

UDP-glucosyltransferaseSteryl glycosyltransferaseSGTUDP-sugar glycosyltransferaseGlycosyltransferase family 1

Inhibition of the transfer of sugar moieties from UDP-sugar donors to acceptor molecules, disrupting fungal cell wall/membrane integrity and detoxification pathways.