Glycosphingolipids in Filamentous Fungi: Biological Roles and Potential Applications in Cosmetics and Health Foods

Abstract

Filamentous fungi are a group of economically important fungi used in the production of fermented foods, industrial enzymes, and secondary metabolites. Glycosphingolipids (GSLs) as constituents of lipid rafts are involved in growth, differentiation, and response to environment stress in filamentous fungi. In addition to these key roles, GSLs are also important in the barrier function of skin to retain moisture as a moisturizing ingredient in cosmetics or health products for their strong biological activity as a functional component. GSLs found in filamentous fungi are divided in two major classes: neutral GSLs (glycosylceramides), glucosylceramides (GlcCers), and/or galactosylceramides (GalCers) and acidic GSLs, mannosylinositol phosphorylceramide (MIPC) and mannosyldiinositol phosphorylceramide [M(IP)₂C]. Glycosylceramides are one of the abundant GSLs in Aspergillus and known to improve skin-barrier function and prevent intestinal impairment as a prebiotic. Some filamentous fungi of Aspergillus spp., synthesizing both GlcCer and GalCer, would be an amenable source to exploit glycosylceramides that wildly adding in cosmetics as moisturizing ingredients or health food as dietary supplements. In this minireview, the types, structures, and biosynthetic pathways of GSLs in filamentous fungi, and the relevance of GSLs in fungal growth, spore formation, and environmental stress response are explained. Furthermore, the advantage, potential development, and application of GlcCer and GalCer from filamentous fungi Aspergillus spp. are also investigate based on the use of plant GlcCer in health foods and cosmetics.

Keywords: Aspergillus; application of glycosylceramide; biosynthetic pathway; filamentous fungi; glucosylceramide and galactosylceramide; glycosphingolipids.

FIGURE 1

Kinds and structures of glycosphingolipid in filamentous fungi. (A) Structure of ceramide; the basic unit of neutral and acidic glycosphingolipids; made up of a LCBs and a FA moiety. (B) Structure of neutral glycosphingolipid which is linked to a sugar residue on the base of ceramide. Neutral glycosphingolipid contains an-OH moiety at C₂ in the FA chain (showed with red ellipse); a double bond between C_4–5 and C_8–9; and a methyl C₉ of the LCB. Monosaccharide may be either glucosyl (Glc) (R1 = OH, R2 = H) or galactosyl (Gal) residues (R1 = H, R2 = OH). (C) The basic structure of acidic glycosphingolipid, inositol phosphorylceramide, is shown. Inositol phosphorylceramide is different from neutral glycosphingolipids in that it contains an additional hydroxy at C₄ of the LCB (showed with green ellipse) and lacks double bonds between C_4–5 and C_8–9, and the C₉ methyl of the LCB. In addition, acidic glycosphingolipids are composed of a very long FA chain (C_18–26) instead of the C_16–18 chain that found in neutral glycosphingolipids.

FIGURE 2

Reorganized biosynthetic pathway of glycosphingolipid in filamentous fungi. The first part (I) involves two key enzyme-catalyzed reactions and is the starting point and common to neutral and acidic GSL synthesis. The second part (II) represents the biosynthetic pathway of neutral GSLs (GlcCer and GalCer) from DhSph including four enzyme-catalyzed reactions. GlcCer and GalCer are the final products of neutral GSL pathway in filamentous fungi. The third part (III) is the biosynthetic process of acidic GSLs, including the production of IPC, MIPC, and M(IP)₂C, which also starts from DhSph and includes three enzyme-catalyzed reactions. IPCs, used as building blocks for more complex molecules, are further modified upon addition of mannose and a second inositol phosphate group to generate MIPC and M(IP)₂C. Red texts represent genes or relative enzymes involved in the GSL pathway. Blue texts indicate the inhibitors of the specific enzyme in the biosynthetic steps.

FIGURE 3

Biological roles of GSLs in filamentous fungi. The effects of GSLs on filamentous fungi were discussed from three aspects, mainly including fungal growth and environmental stress. Meanwhile, the functions of the Δ3-unsaturated FAs, and Δ4, Δ8-unsaturated, and C9-methylated structures of GlcCer and GalCer were also summarized.

FIGURE 4

The potential application diagram of filamentous fungal glycosylceramides, taking A. oryzae as an example. A. oryzae produces GlcCers and GalCers of glycosylceramides which might be safe to add in cosmetics as moisturizing ingredient or health food products as nutritional supplements. A. oryzae glycosylceramides, which function as a prebiotic, have been confirmed to increase ratio of Blautia coccoides and significantly decrease liver cholesterol in obese mice fed with koji glycosylceramide. Monosaccharide may be either glucosyl (Glc) (R1 = OH, R2 = H) or galactosyl (Gal) residues (R1 = H, R2 = OH) in the chemical structure.