title: Different polyamine pathways from bacteria have replaced eukaryotic spermidine biosynthesis in ciliates Tetrahymena thermophila and Paramecium tetaurelia.
abstract: The polyamine spermidine is absolutely required for growth and cell proliferation in eukaryotes, due to its role in post-translational modification of essential translation elongation factor eIF5A, mediated by deoxyhypusine synthase. We have found that free-living ciliates Tetrahymena and Paramecium lost the eukaryotic genes encoding spermidine biosynthesis: S-adenosylmethionine decarboxylase (AdoMetDC) and spermidine synthase (SpdSyn). In Tetrahymena, they were replaced by a gene encoding a fusion protein of bacterial AdoMetDC and SpdSyn, present as three copies. In Paramecium, a bacterial homospermidine synthase replaced the eukaryotic genes. Individual AdoMetDC-SpdSyn fusion protein paralogues from Tetrahymena exhibit undetectable AdoMetDC activity; however, when two paralogous fusion proteins are mixed, AdoMetDC activity is restored and spermidine is synthesized. Structural modelling indicates a functional active site is reconstituted by sharing critical residues from two defective protomers across the heteromer interface. Paramecium was found to accumulate homospermidine, suggesting it replaces spermidine for growth. To test this concept, a budding yeast spermidine auxotrophic strain was found to grow almost normally with homospermidine instead of spermidine. Biosynthesis of spermidine analogue aminopropylcadaverine, but not exogenously provided norspermidine, correlated with some growth. Finally, we found that diverse single-celled eukaryotic parasites and multicellular metazoan Schistosoma worms have lost the spermidine biosynthetic pathway but retain deoxyhypusine synthase.
authors.affiliation: Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Sok Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Food Research, Norwich, UK.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Hanfrey
authors.affiliation: Institute of Food Research, Norwich, UK.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Elliott
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Ealick
authors.affiliation: Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Michael
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics; D002103:Cadaverine / Q000031:analogs & derivatives / Q000096:biosynthesis; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism*; D050939:Gene Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism; D010247:Paramecium / Q000235:genetics* / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012547:Schistosoma / Q000235:genetics; D016415:Sequence Alignment; D013095:Spermidine / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D011436:Spermidine Synthase / Q000235:genetics / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000235:genetics* / Q000378:metabolism*; D015003:Yeasts / Q000187:drug effects / Q000235:genetics / Q000254:growth & development
chemical_list: D011073:Polyamines; C006760:norspermidine; C038448:N-(3-aminopropyl)cadaverine; D000587:Oxidoreductases Acting on CH-NH Group Donors; C063507:deoxyhypusine synthase; D019883:Alkyl and Aryl Transferases; C028376:homospermidine synthetase; D011436:Spermidine Synthase; D012437:Adenosylmethionine Decarboxylase; D002103:Cadaverine; D013095:Spermidine