Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
NCBI PubMed ID: 31046282Publication DOI: 10.1021/acs.joc.9b00544Journal NLM ID: 2985193RPublisher: Columbus, OH: American Chemical Society
Correspondence: Williams SJ <sjwill
unimelb.edu.au>
Institutions: Department of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan, School of Chemistry and Bio21 Institute, University of Melbourne, Parkville, Australia, Department of Molecular Immunology, Research Institute for Microbial Diseases, Suita, Japan
Mincle is a C-type lectin receptor of the innate immune system with the ability to sense pathogens and commensals through lipidic metabolites. While a growing number of bacterial glycolipids have been discovered that can signal through human Mincle, no fungal metabolites are known that can signal through the human form of this receptor. We report the total synthesis of a complex β-1,2-mannosyloxymannitol glycolipid from Malassezia pachydermatis 44-2, which was reported to signal through the murine Mincle receptor. Assembly of 44-2 was achieved through a highly convergent route that exploits symmetry elements inherent within this molecule and delineation of conditions that maintain the delicate L-mannitol triester-triol array. We show that 44-2 is a potent agonist of human Mincle signaling and constitutes the first fungal metabolite identified that can signal through the human Mincle receptor, providing new insights into antifungal immunity.
glycolipid, total synthesis, Mincle receptor, Malassezia pachydermatis
Structure type: oligomer ; 1700.0477 [M+Na]+
C
84H
156O
32Location inside paper: p. 6788, abstract, p. 6789, Fig. 1
Compound class: glycolipid
Contained glycoepitopes: IEDB_133966,IEDB_137485,IEDB_144983,IEDB_144995,IEDB_152206,IEDB_983930,SB_44,SB_72
Methods: 13C NMR, 1H NMR, NMR-2D, chemical synthesis, biological assays, UV, optical rotation measurement, HR-ESI-MS, flash chromatography, HR-ESI-QTOF-MS
Comments, role: solvents in 1H NMR experiments were 95%C5D5N / 5%D2O and 99%CD3OD / 1%CD3COOD
NCBI Taxonomy refs (TaxIDs): 77020
Show glycosyltransferases
NMR conditions: in 99%d8-isopropanol / 1%CD3COOD
1H NMR data: present in publication
|
13C NMR data: present in publication
|
There is only one chemically distinct structure:
Found 
report error