4.8 Article

Convergent evolution of bacterial ceramide synthesis

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NATURE CHEMICAL BIOLOGY
卷 18, 期 3, 页码 305-+

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NATURE PORTFOLIO
DOI: 10.1038/s41589-021-00948-7

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资金

  1. National Science Foundation [MCB-1553004, MCB-2031948]
  2. National Institutes of Health [GM069338, R01AI148366]
  3. Biotechnology and Biological Sciences Research Council [BB/M010996/1, BB/T016841/1]
  4. BBSRC [BB/T016841/1] Funding Source: UKRI

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The bacterial domain produces a variety of sphingolipids with different functions, which play important roles in modulating the host inflammatory system in the human microbiome. Through genomic and biochemical approaches, a complete pathway for bacterial ceramide synthesis was identified, with further discovery of a Gram-positive species capable of producing ceramides. Biochemical evidence suggests that the bacterial ceramide synthesis pathway operates differently from that in eukaryotes, and phylogenetic analyses support the independent evolution of bacterial and eukaryotic ceramide pathways.
The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently.

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