Convergent evolution of bacterial ceramide synthesis
Tóm tắt
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.
Elucidation of the bacterial ceramide biosynthetic pathway reveals that it likely evolved independently from the eukaryotic pathway, as bacteria lack homologs for many of the eukaryotic enzymes and the reactions occur in a different order.
Tài liệu tham khảo
Harrison, P. J., Dunn, T. M. & Campopiano, D. J. Sphingolipid biosynthesis in man and microbes. Nat. Prod. Rep. 35, 921–954 (2018).
Brown, E. M. et al. Bacteroides-derived sphingolipids are critical for maintaining intestinal homeostasis and symbiosis. Cell Host Microbe 25, 668–680 e667 (2019).
Moye, Z. D., Valiuskyte, K., Dewhirst, F. E., Nichols, F. C. & Davey, M. E. Synthesis of sphingolipids impacts survival of Porphyromonas gingivalis and the presentation of surface polysaccharides. Front Microbiol. 7, 1919 (2016).
Stankeviciute, G., Guan, Z., Goldfine, H. & Klein, E. A. Caulobacter crescentus adapts to phosphate starvation by synthesizing anionic glycoglycerolipids and a novel glycosphingolipid. mBio 10, e00107–e00119 (2019).
Ahrendt, T., Wolff, H. & Bode, H. B. Neutral and phospholipids of the Myxococcus xanthus lipodome during fruiting body formation and germination. Appl. Environ. Microbiol. 81, 6538–6547 (2015).
Kaneshiro, E. S., Hunt, S. M. & Watanabe, Y. Bacteriovorax stolpii proliferation and predation without sphingophosphonolipids. Biochem. Biophys. Res. Commun. 367, 21–25 (2008).
Hannun, Y. A. & Obeid, L. M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol. 19, 175–191 (2018).
Merrill, A. H. Jr. Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem. Rev. 111, 6387–6422 (2011).
Ikushiro, H., Hayashi, H. & Kagamiyama, H. A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas paucimobilis EY2395T strain. Purification, characterization, cloning, and overproduction. J. Biol. Chem. 276, 18249–18256 (2001).
Yard, B. A. et al. The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis. J. Mol. Biol. 370, 870–886 (2007).
Geiger, O., Gonzalez-Silva, N., Lopez-Lara, I. M. & Sohlenkamp, C. Amino acid-containing membrane lipids in bacteria. Prog. Lipid Res. 49, 46–60 (2010).
Olea-Ozuna, R. J. et al. Five structural genes required for ceramide synthesis in Caulobacter and for bacterial survival. Environ. Microbiol. 23, 143–159 (2020).
Wadsworth, J. M. et al. The chemical basis of serine palmitoyltransferase inhibition by myriocin. J. Am. Chem. Soc. 135, 14276–14285 (2013).
Harrison, P. J. et al. Use of isotopically labeled substrates reveals kinetic differences between human and bacterial serine palmitoyltransferase. J. Lipid Res. 60, 953–962 (2019).
Li, S., Xie, T., Liu, P., Wang, L. & Gong, X. Structural insights into the assembly and substrate selectivity of human SPT-ORMDL3 complex. Nat. Struct. Mol. Biol. 28, 249–257 (2021).
Raman, M. C. et al. The external aldimine form of serine palmitoyltransferase: structural, kinetic, and spectroscopic analysis of the wild-type enzyme and HSAN1 mutant mimics. J. Biol. Chem. 284, 17328–17339 (2009).
Raman, M. C., Johnson, K. A., Clarke, D. J., Naismith, J. H. & Campopiano, D. J. The serine palmitoyltransferase from Sphingomonas wittichii RW1: an interesting link to an unusual acyl carrier protein. Biopolymers 93, 811–822 (2010).
Ren, J. et al. Quantification of 3-ketodihydrosphingosine using HPLC-ESI-MS/MS to study SPT activity in yeast Saccharomyces cerevisiae. J. Lipid Res. 59, 162–170 (2018).
Zheng, W. et al. Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy. Biochim. Biophys. Acta 1758, 1864–1884 (2006).
Tidhar, R. et al. Eleven residues determine the acyl chain specificity of ceramide synthases. J. Biol. Chem. 293, 9912–9921 (2018).
Chow, T. C. & Schmidt, J. M. Fatty acid composition of Caulobacter crescentus. Microbiology 83, 369–373 (1974).
Okino, N. et al. The reverse activity of human acid ceramidase. J. Biol. Chem. 278, 29948–29953 (2003).
Chen, M., Markham, J. E., Dietrich, C. R., Jaworski, J. G. & Cahoon, E. B. Sphingolipid long-chain base hydroxylation is important for growth and regulation of sphingolipid content and composition in Arabidopsis. Plant Cell 20, 1862–1878 (2008).
Omae, F. et al. DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine. Biochem. J 379, 687–695 (2004).
Price, M. N. et al. Mutant phenotypes for thousands of bacterial genes of unknown function. Nature 557, 503–509 (2018).
Kawahara, K., Moll, H., Knirel, Y. A., Seydel, U. & Zähringer, U. Structural analysis of two glycosphingolipids from the lipopolysaccharide-lacking bacterium Sphingomonas capsulata. Eur. J. Biochem. 267, 1837–1846 (2000).
Feng, Y. & Cronan, J. E. Escherichia coli unsaturated fatty acid synthesis: complex transcription of the fabA gene and in vivo identification of the essential reaction catalyzed by FabB. J. Biol. Chem. 284, 29526–29535 (2009).
Christen, B. et al. The essential genome of a bacterium.Mol. Syst. Biol. 7, https://doi.org/10.1038/msb.2011.58 (2011).
Stankeviciute, G. et al. Differential modes of crosslinking establish spatially distinct regions of peptidoglycan in Caulobacter crescentus. Mol. Microbiol. 111, 995–1008 (2019).
Rocha, F. G. et al. Porphyromonas gingivalis sphingolipid synthesis limits the host inflammatory response. J. Dent. Res. 99, 568–576 (2020).
Mun, J. et al. Structural confirmation of the dihydrosphinganine and fatty acid constituents of the dental pathogen Porphyromonas gingivalis. Org. Biomol. Chem. 5, 3826–3833 (2007).
Nguyen, M. & Vedantam, G. Mobile genetic elements in the genus Bacteroides, and their mechanism(s) of dissemination. Mob. Genet. Elements 1, 187–196 (2011).
Kavanagh, K. L., Jornvall, H., Persson, B. & Oppermann, U. Medium- and short-chain dehydrogenase/reductase gene and protein families: the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell. Mol. Life Sci. 65, 3895–3906 (2008).
Boyden, L. M. et al. Mutations in KDSR cause recessive progressive symmetric erythrokeratoderma. Am. J. Hum. Genet. 100, 978–984 (2017).
Kageyama-Yahara, N. & Riezman, H. Transmembrane topology of ceramide synthase in yeast. Biochem. J 398, 585–593 (2006).
Spassieva, S. et al. Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity. J. Biol. Chem. 281, 33931–33938 (2006).
Liebisch, G. et al. Update on LIPID MAPS classification, nomenclature and shorthand notation for MS-derived lipid structures. J. Lipid Res. 61, 1539–1555 (2020).
Yao, L. et al. A selective gut bacterial bile salt hydrolase alters host metabolism. eLife 7, e37182 (2018).
Lee, M. T., Le, H. H. & Johnson, E. L. Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome. J. Lipid Res. 62, 100034 (2021).
Tudzynski, B. Gibberellin biosynthesis in fungi: genes, enzymes, evolution, and impact on biotechnology. Appl. Microbiol. Biotechnol. 66, 597–611 (2005).
Huang, R., O’Donnell, A. J., Barboline, J. J. & Barkman, T. J. Convergent evolution of caffeine in plants by co-option of exapted ancestral enzymes. Proc. Natl Acad. Sci. USA 113, 10613–10618 (2016).
Dick, R. et al. Comparative analysis of benzoxazinoid biosynthesis in monocots and dicots: independent recruitment of stabilization and activation functions. Plant Cell 24, 915–928 (2012).
Kawasaki, S. et al. The cell envelope structure of the lipopolysaccharide-lacking gram-negative bacterium Sphingomonas paucimobilis. J. Bacteriol. 176, 284–290 (1994).
Poindexter, J. S. Selection for nonbuoyant morphological mutants of Caulobacter crescentus. J. Bacteriol. 135, 1141–1145 (1978).
Ferrieres, L. et al. Silent mischief: bacteriophage Mu insertions contaminate products of Escherichia coli random mutagenesis performed using suicidal transposon delivery plasmids mobilized by broad-host-range RP4 conjugative machinery. J. Bacteriol. 192, 6418–6427 (2010).
Martinez-Garcia, E., Calles, B., Arevalo-Rodriguez, M. & de Lorenzo, V. pBAM1: an all-synthetic genetic tool for analysis and construction of complex bacterial phenotypes. BMC Microbiol. 11, 38 (2011).
Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959).
Guan, Z., Katzianer, D., Zhu, J. & Goldfine, H. Clostridium difficile contains plasmalogen species of phospholipids and glycolipids. Biochim. Biophys. Acta 1842, 1353–1359 (2014).
Edgar, R. C. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinf. 5, 113 (2004).
Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30, 1312–1313 (2014).
Miller, M. A., Pfeiffer, W. & Schwartz, T. Creating the CIPRES Science Gateway for inference of large phylogenetic trees. In Proc. 2010 Gateway Computing Environments Workshop (GCE), 1–8 (2010).
Chamberlain, S. A. & Szocs, E. taxize: taxonomic search and retrieval in R. F1000Res. 2, 191 (2013).
Yu, G. Using ggtree to visualize data on tree-like structures. in Curr. Protoc. Bioinformatics 69, e96 (IEEE, 2020).
Paradis, E. & Schliep, K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 35, 526–528 (2019).
Wang, L. G. et al. Treeio: an R Package for phylogenetic tree input and output with richly annotated and associated data. Mol. Biol. Evol. 37, 599–603 (2020).
Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer-Verlag, 2016).
Madeira, F. et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 47, W636–W641 (2019).
Lowther, J. et al. Role of a conserved arginine residue during catalysis in serine palmitoyltransferase. FEBS Lett. 585, 1729–1734 (2011).