Sterylglucosides in Fungi

Abstract

Sterylglucosides (SGs) are sterol conjugates widely distributed in nature. Although their universal presence in all living organisms suggests the importance of this kind of glycolipids, they are yet poorly understood. The glycosylation of sterols confers a more hydrophilic character, modifying biophysical properties of cell membranes and altering immunogenicity of the cells. In fungi, SGs regulate different cell pathways to help overcome oxygen and pH challenges, as well as help to accomplish cell recycling and other membrane functions. At the same time, the level of these lipids is highly controlled, especially in wild-type fungi. In addition, modulating SGs metabolism is becoming a novel tool for vaccine and antifungal development. In the present review, we bring together multiple observations to emphasize the underestimated importance of SGs for fungal cell functions.

Keywords: Aspergillus; Candida; Cryptococcus; fungi; glycolipid; sterol; sterol glucosyltransferase; sterylglucosidase; sterylglucoside; ß-glucosidase.

Figure 1

Schematic overview of conjugated sterol metabolism in fungi. The chemical structure of free and conjugated sterols sterylglucosides (SG), acyl Sterylglucosides (ASG), and sterol esters (SE). Dashed arrows indicate multiple steps. The position of the enzymes sterol glycosyltransferase (SGT) and sterylglucosidase (SGL) is indicated. SGs are characterized by having a sugar linked to the C3 hydroxyl group of the sterol moiety through a β-glycosidic bond. ASGs are derivatives of SGs in which the hydroxyl group of the C6 position of the sugar moiety is acylated by sterol glycoside acyltransferase (SGA), however, no SGA has been characterized in fungi to date. Gray arrows represent enzymatic pathways still to be characterized. In SEs the hydroxyl group at the C3 position is esterified with a fatty acid by sterol O-acyltransferases, named Are1 and Are2 in Saccharomyces cerevisiae, which catalyzes the formation of sterol esters and act in concert with the sterol ester hydrolases Yeh1, Yeh2, and Tgl1.

Figure 2

SGL1 homologs structural comparison. (A) Cryptococcus neoformans Sgl1 structure (PDB: 7LPO) with ergosterol 3β-D-glucoside (gray) docked in the active site. (B) Fusarium oxysporum (orange) and Paracoccidioides lutzii (cyan) Alphafold models superposed on Sgl1 (pink) structure. (C) The residues on the glucose binding site are conserved in a similar position in F. oxysporum and P. lutzzi models. Sgl1 residues are shown in pink.