Ferroptosis Related Immunomodulatory Effect of a Novel Extracellular Polysaccharides from Marine Fungus Aureobasidium melanogenum

Abstract

Marine fungi represent an important and sustainable resource, from which the search for novel biological substances for application in the pharmacy or food industry offers great potential. In our research, novel polysaccharide (AUM-1) was obtained from marine Aureobasidium melanogenum SCAU-266 were obtained and the molecular weight of AUM-1 was determined to be 8000 Da with 97.30% of glucose, 1.9% of mannose, and 0.08% galactose, owing to a potential backbone of α-D-Glcp-(1→2)-α-D-Manp-(1→4)-α-D-Glcp-(1→6)-(SO3−)-4-α-D-Glcp-(1→6)-1-β-D-Glcp-1→2)-α-D-Glcp-(1→6)-β-D-Glcp-1→6)-α-D-Glcp-1→4)-α-D-Glcp-6→1)-[α-D-Glcp-4]26→1)-α-D-Glcp and two side chains that consisted of α-D-Glcp-1 and α-D-Glcp-(1→6)-α-D-Glcp residues. The immunomodulatory effect of AUM-1 was identified. Then, the potential molecular mechanism by which AUM-1 may be connected to ferroptosis was indicated by metabonomics, and the expression of COX2, SLC7A11, GPX4, ACSL4, FTH1, and ROS were further verified. Thus, we first speculated that AUM-1 has a potential effect on the ferroptosis-related immunomodulatory property in RAW 264.7 cells by adjusting the expression of GPX4, regulated glutathione (oxidative), directly causing lipid peroxidation owing to the higher ROS level through the glutamate metabolism and TCA cycle. Thus, the ferroptosis related immunomodulatory effect of AUM-1 was obtained.

Exopolysaccharides from Marine Microbes: Source, Structure and Application

“…The molecular weight can be determined by high-performance gel-permeation chromatography (HPGPC), combined with differential detector (ID) or multi-angle laser light scattering (MALS) [ 71 ]. Furthermore, through the data of the Fourier-Transform infrared spectroscopy (FTIR), methylation analysis, and nuclear magnetic resonance (NMR), the glycosidic bond-linking types and main functional groups can be obtained [ 26 , 72 , 73 , 74 ].…”

“…Recently, a novel EPS (AUM-1) with immunomodulatory activity was obtained from the marine Aureobasidium melanogenum SCAU-266. The AUM-1 with a molecular weight of 8000 Da had a main monosaccharide of Glc (97.30%), whose structure possessed a potential backbone of α-D-Glcp-(1→2)-α-D-Man p -(1→4)-α-D-Glc p -(1→6)-(-(SO 3 − )-4-α-D-Glc p -(1→6)-1-β-D-Glc p -1→2)-α-D-Glc p -(1→6)-β-D-Glc p -1→6)-α-D-Glc p -1→4)-α-D-Glc p -6→1)-[α-D-Glc p -4] 26 →1)-α-D-Glc p [ 74 ]. The possible structure of these marine fungal EPS mentioned in Table 2 are shown in Figure 1 .…”

“…When the immunity is impaired, it will lead to various adverse immune reactions [ 137 ]. Several of the EPS synthesized by marine microorganisms have immunomodulatory activities [ 45 , 60 , 61 , 74 , 138 , 139 , 140 ]. For example, an EPS named as EPS2E1 was extracted from marine Halomonas sp.…”

“…Recently, a novel EPS (AUM-1) was obtained from marine Aureobasidium melanogenum SCAU-266, with a potential effect on the ferroptosis-related immunomodulatory property in RAW264.7 cells. The mechanism studies have shown that it can adjust the expression of GPX4, regulate glutathione (oxidative), and directly cause lipid peroxidation, due to the higher ROS level by the glutamate metabolism and TCA cycle ( Figure 3 ) [ 74 ].…”

“… Structures of several EPS, isolated from marine fungi in the last decade [ 74 , 83 , 84 , 85 , 86 , 87 , 88 ]. ( a ) EPS from Penicillium solitum ; ( b ) EPS from Aspergillus versicolor ; ( c ) EPS from Fusarium oxysporum ; ( d ) EPS from Alternaria sp.…”