Identification and Biosynthesis of Pro-Inflammatory Sulfonolipids from an Opportunistic Pathogen Chryseobacterium gleum .

Autor: Hou L; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.; Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China., Tian HY; College of Pharmacy, Jinan University, Guangzhou 510632, China., Wang L; College of Pharmacy, Jinan University, Guangzhou 510632, China., Ferris ZE; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States., Wang J; Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, United States., Cai M; Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China., Older EA; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States., Raja MRK; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29209, United States., Xue D; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States., Sun W; College of Pharmacy, Jinan University, Guangzhou 510632, China., Nagarkatti P; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, United States., Nagarkatti M; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, United States., Chen H; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29209, United States., Fan D; Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, United States., Tang X; Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China., Li J; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.
Jazyk: angličtina
Zdroj: ACS chemical biology [ACS Chem Biol] 2022 May 20; Vol. 17 (5), pp. 1197-1206. Date of Electronic Publication: 2022 Apr 27.
DOI: 10.1021/acschembio.2c00141
Abstrakt: Sulfonolipids (SoLs) are a unique class of sphingolipids featuring a sulfonate group compared to other sphingolipids. However, the biological functions and biosynthesis of SoLs in human microbiota have been poorly understood. Here, we report the discovery and isolation of SoLs from a human opportunistic pathogen Chryseobacterium gleum DSM16776. We show for the first time the pro-inflammatory activity of SoLs with mice primary macrophages. Furthermore, we used both in vivo heterologous expression and in vitro biochemical reconstitution to characterize two enzymes, cysteate synthase and cysteate fatty acyltransferase, that are specifically involved in the biosynthesis of SoLs rather than other sphingolipids. Based on these two SoL-specific enzymes, our bioinformatics analysis showed a wider distribution of SoL biosynthetic genes in microbes that had not been reported as SoL producers. We selected four of these strains and verified their cysteate synthase and cysteate fatty acyltransferase activities in SoL biosynthesis. Considering this wider distribution of SoL-specific biosynthetic enzymes in the context of SoLs' activity in mediating inflammation, a common and fundamental biological process, it may suggest a more comprehensive function of SoLs at play.
Databáze: MEDLINE
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