Exploring new biocatalysts for the sphingolipid synthesis in actinobacteria Gustavo Perez Ortiz 1 , Sam Mathew 1 , Eric A. Klein 2 , Paul A. Hoskisson 3 , Dominic J. Campopiano 1 1 The University of Edinburgh, UK, 2 Rutgers University-Camden, USA, 3 University of Strathclyde, UK Due to their important roles in human health and disease, the eukaryotic biosynthesis pathway of sphingolipids has been described in detail 1 . By contrast, this class of lipids has been identified in only a handful of bacterial taxa 2 . Bacteria do not appear to have homologous enzymes, except for serine palmitoyltransferase (SPT) that performs the initial conserved step in ceramide synthesis 3 . The presence of putative spt genes is a good indication that a bacterial species may synthesize sphingolipids 4 . However, the presence of a predicted SPT alone is not enough because of the high similarity between members of the larger family of pyridoxal 5’-phosphate (PLP)-dependent α-oxoamine synthases (AOS) that are also involved in heme and biotin synthesis 2 . Recently, our research group identified the remaining genes of the ceramide biosynthetic pathway in Caulobacter crescentus and found the order of the steps to be different to that found in eukaryotes 5 . The importance of these genes was corroborated by an independent group 6 . The characterization of the bacterial ceramide biosynthetic pathway enabled a bioinformatic screen that led to the identification of 17 taxonomic classes, including Actinobacteria, suggesting that bacterial sphingolipid synthesis occurs across a wide range of organisms 5 . Here, we characterized the first Actinobacterial SPT from Streptomyces aurantiacus (Sa-SPT) in vitro , we explore the lipid profile of the organism, the physiological roles for sphingolipids in actinobacteria and identify the evolutionary differences between the bacterial and eukaryotic pathways. References 1. Y. A. Hannun and L. M. Obeid, Nat Rev Mol Cell Biol , 2018, 19 , 175-191. 2. P. J. Harrison, T. M. Dunn and D. J. Campopiano, Nat Prod Rep , 2018, 35 , 921-954. 3. B. A. Yard, L. G. Carter, K. A. Johnson, I. M. Overton, M. Dorward, H. Liu, S. A. McMahon, M. Oke, D. Puech, G. J. Barton, J. H. Naismith and D. J. Campopiano, J Mol Biol , 2007, 370 , 870-886. 4. O. Geiger, N. González-Silva, I. M. López-Lara and C. Sohlenkamp, Prog Lipid Res , 2010, 49 , 46-60. 5. G. Stankeviciute, P. Tang, B. Ashley, J. D. Chamberlain, M. E. B. Hansen, A. Coleman, R. D'Emilia, L. Fu, E. C. Mohan, H. Nguyen, Z. Guan, D. J. Campopiano and E. A. Klein, Nat Chem Biol , 2021, DOI: 10.1038/s41589-021-00948-7. 6. R. J. Olea-Ozuna, S. Poggio, EdBergstrom, E. Quiroz-Rocha, D. A. Garcia-Soriano, D. X. Sahonero-Canavesi, J. Padilla- Gomez, L. Martinez-Aguilar, I. M. Lopez-Lara, J. Thomas-Oates and O. Geiger, Environ Microbiol , 2021, 23 , 143-159.
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