{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T17:22:43Z","timestamp":1774545763107,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["PR905\/19-1"],"award-info":[{"award-number":["PR905\/19-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["TE599\/9-1"],"award-info":[{"award-number":["TE599\/9-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["PR905\/20-1"],"award-info":[{"award-number":["PR905\/20-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["NG170\/1-1"],"award-info":[{"award-number":["NG170\/1-1"]}]},{"name":"German Academic Exchange Service (DAAD)","award":["PR905\/19-1"],"award-info":[{"award-number":["PR905\/19-1"]}]},{"name":"German Academic Exchange Service (DAAD)","award":["TE599\/9-1"],"award-info":[{"award-number":["TE599\/9-1"]}]},{"name":"German Academic Exchange Service (DAAD)","award":["PR905\/20-1"],"award-info":[{"award-number":["PR905\/20-1"]}]},{"name":"German Academic Exchange Service (DAAD)","award":["NG170\/1-1"],"award-info":[{"award-number":["NG170\/1-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>S-adenosylmethionine synthetase (SAMS) is a key enzyme for the synthesis of the lone methyl donor S-adenosyl methionine (SAM), which is involved in transmethylation reactions and hence required for cellular processes such as DNA, RNA, and histone methylation, but also polyamine biosynthesis and proteostasis. In the human malaria parasite Plasmodium falciparum, PfSAMS is encoded by a single gene and has been suggested to be crucial for malaria pathogenesis and transmission; however, to date, PfSAMS has not been fully characterized. To gain deeper insight into the function of PfSAMS, we generated a conditional gene knockdown (KD) using the glmS ribozyme system. We show that PfSAMS localizes to the cytoplasm and the nucleus of blood-stage parasites. PfSAMS-KD results in reduced histone methylation and leads to impaired intraerythrocytic growth and gametocyte development. To further determine the interaction network of PfSAMS, we performed a proximity-dependent biotin identification analysis. We identified a complex network of 1114 proteins involved in biological processes such as cell cycle control and DNA replication, or transcription, but also in phosphatidylcholine and polyamine biosynthesis and proteasome regulation. Our findings highlight the diverse roles of PfSAMS during intraerythrocytic growth and sexual stage development and emphasize that PfSAMS is a potential drug target.<\/jats:p>","DOI":"10.3390\/microorganisms10071419","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T01:57:11Z","timestamp":1657850231000},"page":"1419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Plasmodium falciparum S-Adenosylmethionine Synthetase Is Essential for Parasite Survival through a Complex Interaction Network with Cytoplasmic and Nuclear Proteins"],"prefix":"10.3390","volume":"10","author":[{"given":"Jean Pierre","family":"Musabyimana","sequence":"first","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-6384","authenticated-orcid":false,"given":"Ute","family":"Distler","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Institute of Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane","family":"Sassmannshausen","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Berks","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Manti","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Bennink","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-2793","authenticated-orcid":false,"given":"Lea","family":"Blaschke","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul-Christian","family":"Burda","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology (CSSB) c\/o DESY, Bernhard Nocht Institute, University of Hamburg, Notkestra\u00dfe 85, Building 15, 22607 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ansgar","family":"Flammersfeld","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-0017","authenticated-orcid":false,"given":"Stefan","family":"Tenzer","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Institute of Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Che Julius","family":"Ngwa","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-5558","authenticated-orcid":false,"given":"Gabriele","family":"Pradel","sequence":"additional","affiliation":[{"name":"Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1357-2725(99)00139-9","article-title":"S-Adenosylmethionine","volume":"32","author":"Lu","year":"2000","journal-title":"Int. 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