{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:18Z","timestamp":1785432378171,"version":"3.56.0"},"reference-count":94,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research","award":["P20225HFSK"],"award-info":[{"award-number":["P20225HFSK"]}]},{"name":"Ministry of University and Research","award":["D53D230 22580001"],"award-info":[{"award-number":["D53D230 22580001"]}]},{"name":"Ministry of University and Research","award":["H53D23011040001"],"award-info":[{"award-number":["H53D23011040001"]}]},{"award":["P20225HFSK"],"award-info":[{"award-number":["P20225HFSK"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]},{"award":["D53D230 22580001"],"award-info":[{"award-number":["D53D230 22580001"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]},{"award":["H53D23011040001"],"award-info":[{"award-number":["H53D23011040001"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cysteine biosynthesis is increasingly recognized as a critical determinant of bacterial virulence, highlighting this pathway as a promising reservoir of novel antimicrobial targets. In Pseudomonas aeruginosa, however, the molecular basis of cysteine production has only recently begun to emerge. Here, we identify PA3816 as the major P. aeruginosa serine acetyltransferase (PaCysE), the enzyme responsible for generating the activated serine intermediate that feeds O-acetylserine sulfhydrylase-mediated cysteine synthesis. Through a combination of biochemical and genetic approaches, we demonstrate that PaCysE efficiently catalyzes L-serine acetylation in vitro, and in turn, deletion mutants exhibit cysteine auxotrophy, underscoring its essential contribution to O-acetylserine production. Notably, PaCysE is less sensitive to feedback inhibition by cysteine and does not appear to form the canonical cysteine synthase complex, suggesting a regulatory architecture that diverges from well-characterized orthologs. Loss of PaCysE function has broad physiological consequences, including enhanced biofilm formation, reduced pyocyanin production, and attenuated infectivity in an animal model, linking cysteine biosynthesis directly to pathogen fitness. Finally, we identify a thiazole derivative that inhibits PaCysE activity (IC50 \u2248 30 \u00b5M) and suppresses bacterial growth in a cysteine-dependent manner, providing a proof-of-concept for therapeutically targeting this pathway.<\/jats:p>","DOI":"10.3390\/ijms27115091","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"5091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serine Acetyltransferase from Pseudomonas aeruginosa: Distinctive Features, Pleiotropic Roles, and Therapeutic Potential"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6605-0818","authenticated-orcid":false,"given":"Francesco","family":"Guggino","sequence":"first","affiliation":[{"name":"Interdepartmental Center Siteia, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-4610","authenticated-orcid":false,"given":"Sarah","family":"Hijazi","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7339-2459","authenticated-orcid":false,"given":"Rebecca","family":"Marted\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3115-2122","authenticated-orcid":false,"given":"Valeria","family":"Buoli Comani","sequence":"additional","affiliation":[{"name":"Interdepartmental Center Biopharmanet-TEC, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5699-2516","authenticated-orcid":false,"given":"Jole Maria Lucia","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-8858","authenticated-orcid":false,"given":"Omar","family":"De Bei","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9629-6966","authenticated-orcid":false,"given":"Giannamaria","family":"Annunziato","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-3712","authenticated-orcid":false,"given":"Marco","family":"Pieroni","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1407-8274","authenticated-orcid":false,"given":"Gabriele","family":"Costantino","sequence":"additional","affiliation":[{"name":"Department of Food and Drug, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6787-0594","authenticated-orcid":false,"given":"Stefano","family":"Bettati","sequence":"additional","affiliation":[{"name":"Interdepartmental Center Siteia, University of Parma, 43124 Parma, Italy"},{"name":"Interdepartmental Center Biopharmanet-TEC, University of Parma, 43124 Parma, Italy"},{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-6786","authenticated-orcid":false,"given":"Marialaura","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5619-7912","authenticated-orcid":false,"given":"Emanuela","family":"Frangipani","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-0627","authenticated-orcid":false,"given":"Barbara","family":"Campanini","sequence":"additional","affiliation":[{"name":"Interdepartmental Center Biopharmanet-TEC, University of Parma, 43124 Parma, Italy"},{"name":"Department of Food and Drug, University of Parma, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.csbj.2025.02.015","article-title":"Identification of Novel Inhibitors Targeting Serine Acetyltransferase from Neisseria Gonorrhoeae","volume":"27","author":"Oldham","year":"2025","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.tim.2023.06.010","article-title":"Cysteine and Resistance to Oxidative Stress: Implications for Virulence and Antibiotic Resistance","volume":"32","author":"Tikhomirova","year":"2024","journal-title":"Trends Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00808-20","DOI":"10.1128\/IAI.00808-20","article-title":"Brucella Ovis Cysteine Biosynthesis Contributes to Peroxide Stress Survival and Fitness in the Intracellular Niche","volume":"89","author":"Varesio","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.1128\/AEM.00157-15","article-title":"CysK Plays a Role in Biofilm Formation and Colonization by Vibrio Fischeri","volume":"81","author":"Singh","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"116461","DOI":"10.1016\/j.ejmech.2024.116461","article-title":"Targeting the Cysteine Biosynthesis Pathway in Microorganisms: Mechanism, Structure, and Drug Discovery","volume":"271","author":"Tao","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kredich, N.M. (2008). Biosynthesis of Cysteine. EcoSal Plus, 3.","DOI":"10.1128\/ecosalplus.3.6.1.11"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/prot.70107","article-title":"The Curious Case of CysE: Diversity and Distribution of Serine Acetyltransferases in Bacteria","volume":"94","author":"Oldham","year":"2025","journal-title":"Proteins"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1107\/S0907444904015240","article-title":"Structure of Serine Acetyltransferase from Haemophilus Influenzae Rd","volume":"60","author":"Gorman","year":"2004","journal-title":"Acta Cryst. D"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.abb.2004.06.006","article-title":"Kinetic Mechanism of the Serine Acetyltransferase from Haemophilus Influenzae","volume":"429","author":"Johnson","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1021\/bi0358521","article-title":"Structure of Serine Acetyltransferase in Complexes with CoA and Its Cysteine Feedback Inhibitor","volume":"43","author":"Olsen","year":"2004","journal-title":"Biochemistry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1042\/bj20030429","article-title":"Serine Acetyltransferase of Escherichia coli: Substrate Specificity and Feedback Control by Cysteine","volume":"375","author":"Hindson","year":"2003","journal-title":"Biochem. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40729","DOI":"10.1074\/jbc.M403751200","article-title":"The Structure and Mechanism of Serine Acetyltransferase from Escherichia coli","volume":"279","author":"Pye","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/1873-3468.12630","article-title":"Modulation of Escherichia coli Serine Acetyltransferase Catalytic Activity in the Cysteine Synthase Complex","volume":"591","author":"Benoni","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.molbiopara.2008.09.006","article-title":"Isoform-Dependent Feedback Regulation of Serine O-Acetyltransferase Isoenzymes Involved in l-Cysteine Biosynthesis of Entamoeba histolytica","volume":"163","author":"Hussain","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1042\/BCJ20210564","article-title":"Serine Acetyltransferase from Neisseria Gonorrhoeae; Structural and Biochemical Basis of Inhibition","volume":"479","author":"Oldham","year":"2022","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.ijbiomac.2019.10.170","article-title":"Allosteric Inhibition and Kinetic Characterization of Klebsiella pneumoniae CysE: An Emerging Drug Target","volume":"151","author":"Verma","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/j.bbapap.2014.07.009","article-title":"Crystal Structure of Serine Acetyl Transferase from Brucella Abortus and Its Complex with Coenzyme A","volume":"1844","author":"Kumar","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12533","DOI":"10.1074\/jbc.M110.197376","article-title":"Structural and Biochemical Studies of Serine Acetyltransferase Reveal Why the Parasite Entamoeba Histolytica Cannot Form a Cysteine Synthase Complex","volume":"286","author":"Kumar","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1021\/bi00175a040","article-title":"Kinetic Mechanism of Serine Transacetylase from Salmonella typhimurium","volume":"33","author":"Leu","year":"1994","journal-title":"Biochemistry"},{"key":"ref_20","first-page":"453","article-title":"Overproduction of L-Cysteine and L-Cystine by Expression of Genes for Feedback Inhibition-Insensitive Serine Acetyltransferase from Arabidopsis thaliana in Escherichia coli","volume":"179","author":"Takagi","year":"1999","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100098","DOI":"10.1016\/j.mcpro.2021.100098","article-title":"Revealing the Dynamic Allosteric Changes Required for Formation of the Cysteine Synthase Complex by Hydrogen-Deuterium Exchange MS","volume":"20","author":"Rosa","year":"2021","journal-title":"Mol. Cell. Proteom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1016\/S0021-9258(19)78241-6","article-title":"Purification and Characterization of Cysteine Synthetase, a Bifunctional Protein Complex, from Salmonella typhimurium","volume":"244","author":"Kredich","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.bbrc.2006.01.054","article-title":"On the Interaction Site of Serine Acetyltransferase in the Cysteine Synthase Complex from Escherichia coli","volume":"341","author":"Zhao","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7610","DOI":"10.1128\/JB.186.22.7610-7617.2004","article-title":"Role of CysE in Production of an Extracellular Signaling Molecule in Providencia Stuartii and Escherichia coli: Loss of cysE Enhances Biofilm Formation in Escherichia coli","volume":"186","author":"Sturgill","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00389-17","DOI":"10.1128\/JB.00389-17","article-title":"Thiol Starvation Induces Redox-Mediated Dysregulation of Escherichia coli Biofilm Components","volume":"200","author":"Hufnagel","year":"2018","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.resmic.2010.06.004","article-title":"Cysteine Biosynthesis, Oxidative Stress and Antibiotic Resistance in Salmonella typhimurium","volume":"161","author":"Turnbull","year":"2010","journal-title":"Res. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s42003-025-08670-z","article-title":"The Acetyltransferase CysE Modulates Virulence and Drug Resistance of Mycobacterium tuberculosis by Interfering with Oxidative Stress Responses","volume":"8","author":"Zhang","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00159-17","DOI":"10.1128\/JB.00159-17","article-title":"Cysteine Biosynthesis Controls Serratia marcescens Phospholipase Activity","volume":"199","author":"Anderson","year":"2017","journal-title":"J. Bacteriol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1128\/IAI.01423-15","article-title":"Genes Required for the Fitness of Salmonella enterica Serovar Typhimurium during Infection of Immunodeficient Gp91-\/- Phox Mice","volume":"84","author":"Grant","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"BSR20220368","DOI":"10.1042\/BSR20220368","article-title":"Combatting Antimicrobial Resistance via the Cysteine Biosynthesis Pathway in Bacterial Pathogens","volume":"42","author":"Hicks","year":"2022","journal-title":"Biosci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e14573","DOI":"10.1111\/cbdd.14573","article-title":"Advancements in Inhibitors of Crucial Enzymes in the Cysteine Biosynthetic Pathway: Serine Acetyltransferase and O-Acetylserine Sulfhydrylase","volume":"104","author":"Qin","year":"2024","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100443","DOI":"10.1016\/j.rechem.2022.100443","article-title":"Exploring the Chemical Space around N-(5-Nitrothiazol-2-Yl)-1,2,3-Thiadiazole-4-Carboxamide, a Hit Compound with Serine Acetyltransferase (SAT) Inhibitory Properties","volume":"4","author":"Pavone","year":"2022","journal-title":"Results Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Toyomoto, T., Ono, K., Shiba, T., Momitani, K., Zhang, T., Tsutsuki, H., Ishikawa, T., Hoso, K., Hamada, K., and Rahman, A. (2023). Alkyl Gallates Inhibit Serine O-Acetyltransferase in Bacteria and Enhance Susceptibility of Drug-Resistant Gram-Negative Bacteria to Antibiotics. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1276447"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rahman, A., Ono, K., Toyomoto, T., Hanaoka, K., and Sawa, T. (2025). Identification of Fungal Metabolite Gliotoxin as a Potent Inhibitor Against Bacterial O-Acetylserine Sulfhydrylase CysK and CysM. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031106"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.biochi.2024.01.009","article-title":"Multi-Oligomeric and Catalytically Compromised Serine Acetyltransferase and Cysteine Regulatory Complex of Mycobacterium tuberculosis","volume":"221","author":"Rahisuddin","year":"2024","journal-title":"Biochimie"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1021\/acsmedchemlett.9b00627","article-title":"Inhibition of Nonessential Bacterial Targets: Discovery of a Novel Serine O -Acetyltransferase Inhibitor","volume":"11","author":"Franko","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e0154","DOI":"10.1199\/tab.0154","article-title":"Molecular Biology, Biochemistry and Cellular Physiology of Cysteine Metabolism in Arabidopsis thaliana","volume":"9","author":"Hell","year":"2011","journal-title":"Arab. Book"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Li, S., Ji, C., Zhou, Y., Li, C., and Wang, W. (2021). Genetic Variation of the Serine Acetyltransferase Gene Family for Sulfur Assimilation in Maize. Genes, 12.","DOI":"10.3390\/genes12030437"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2.3.1","DOI":"10.1002\/0471250953.bi0203s00","article-title":"Multiple Sequence Alignment Using ClustalW and ClustalX","volume":"00","author":"Thompson","year":"2003","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W320","DOI":"10.1093\/nar\/gku316","article-title":"Deciphering Key Features in Protein Structures with the New ENDscript Server","volume":"42","author":"Robert","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"114304","DOI":"10.1016\/j.isci.2025.114304","article-title":"De Novo Cysteine Biosynthesis in Pseudomonas aeruginosa: Characterization of the Two Main Cysteine Synthase Isoforms","volume":"29","author":"Sassi","year":"2026","journal-title":"iScience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1099\/00221287-115-2-513","article-title":"Cysteine Auxotrophs of Salmonella typhimurium Which Grow without Cysteine in a Hydrogen\/Carbon Dioxide Atmosphere","volume":"115","author":"Barrett","year":"1979","journal-title":"J. Gen. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1042\/bj1100597","article-title":"Positive Control of Sulphate Reduction in Escherichia coli. The Nature of the Pleiotropic Cysteineless Mutants of E. Coli K12","volume":"110","year":"1968","journal-title":"Biochem. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1574-6968.1997.tb10286.x","article-title":"Identification of the Serine Acetyltransferase Gene of Staphylococcus xylosus","volume":"148","author":"Fiegler","year":"1997","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1574-6968.2005.00068.x","article-title":"Functional Analysis of L-Serine O-Acetyltransferase from Corynebacterium glutamicum","volume":"255","author":"Haitani","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e00155-18","DOI":"10.1128\/mSphere.00155-18","article-title":"Pseudomonas aeruginosa gshA Mutant Is Defective in Biofilm Formation, Swarming, and Pyocyanin Production","volume":"3","author":"Esani","year":"2018","journal-title":"mSphere"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.molmed.2004.10.002","article-title":"The Role of Pyocyanin in Pseudomonas aeruginosa Infection","volume":"10","author":"Lau","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/mmi.14132","article-title":"Both Toxic and Beneficial Effects of Pyocyanin Contribute to the Lifecycle of Pseudomonas aeruginosa","volume":"110","author":"Meirelles","year":"2018","journal-title":"Mol. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"128429","DOI":"10.1016\/j.micres.2025.128429","article-title":"The Post-Transcriptional Regulator RsmA Mediates the Protective Response against Pyocyanin Overproduction in Pseudomonas aeruginosa, as Revealed by a Proteomic Approach","volume":"305","year":"2026","journal-title":"Microbiol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Higgins, S., Heeb, S., Rampioni, G., Fletcher, M.P., Williams, P., and C\u00e1mara, M. (2018). Differential Regulation of the Phenazine Biosynthetic Operons by Quorum Sensing in Pseudomonas aeruginosa PAO1-N. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00252"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Jim\u00e9nez, A., Llamas, M.A., and Marcos-Torres, F.J. (2023). Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511895"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Thees, A.V., Pietrosimone, K.M., Melchiorre, C.K., Marden, J.N., Graf, J., Lynes, M.A., and Maltz-Matyschsyk, M. (2021). PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.789765"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113973","DOI":"10.1016\/j.isci.2025.113973","article-title":"Exploring Reductive Stress as a Regulation Approach for Pseudomonas aeruginosa Biofilm","volume":"28","author":"Liu","year":"2025","journal-title":"iScience"},{"key":"ref_54","first-page":"e2437","article-title":"Microtiter Dish Biofilm Formation Assay","volume":"47","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1128\/JB.00410-15","article-title":"Cyclic Di-GMP Signaling Contributes to Pseudomonas aeruginosa-Mediated Catheter-Associated Urinary Tract Infection","volume":"198","author":"Cole","year":"2016","journal-title":"J. Bacteriol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-micro-020518-115555","article-title":"Multiple Roles of C-Di-GMP Signaling in Bacterial Pathogenesis","volume":"73","author":"Valentini","year":"2019","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100335","DOI":"10.1016\/j.bioflm.2025.100335","article-title":"Inactivation of Cysteine Synthase CysK-A Enhances Flocculation, Biofilm Formation, and Sensitivity to Oxidative Stress in Azospirillum brasilense Sp7","volume":"11","author":"Ojeda","year":"2026","journal-title":"Biofilm"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1099\/00221287-148-4-923","article-title":"Genetically Programmed Autoinducer Destruction Reduces Virulence Gene Expression and Swarming Motility in Pseudomonas aeruginosa PAO1","volume":"148","author":"Reimmann","year":"2002","journal-title":"Microbiology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e4967","DOI":"10.1002\/pro.4967","article-title":"KCD: A Prediction Web Server of Knowledge-Based Circular Dichroism","volume":"33","year":"2024","journal-title":"Protein Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"BSR20210336","DOI":"10.1042\/BSR20210336","article-title":"A Meta-Analysis of the Activity, Stability, and Mutational Characteristics of Temperature-Adapted Enzymes","volume":"41","author":"Gault","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1271\/bbb.65.865","article-title":"Increase in the Stability of Serine Acetyltransferase from Escherichia coli against Cold Inactivation and Proteolysis by Forming a Bienzyme Complex","volume":"65","author":"Mino","year":"2001","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21102","DOI":"10.1074\/jbc.M112.359737","article-title":"Staphylococcus aureus CymR Is a New Thiol-Based Oxidation-Sensing Regulator of Stress Resistance and Oxidative Response","volume":"287","author":"Ji","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.1073\/pnas.0702081104","article-title":"A Complex Thiolate Switch Regulates the Bacillus Subtilis Organic Peroxide Sensor OhrR","volume":"104","author":"Lee","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/nsmb856","article-title":"Redox Regulation of OxyR Requires Specific Disulfide Bond Formation Involving a Rapid Kinetic Reaction Path","volume":"11","author":"Lee","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1093\/bioinformatics\/btw514","article-title":"PRODIGY: A Web Server for Predicting the Binding Affinity of Protein\u2013Protein Complexes","volume":"32","author":"Xue","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Honorato, R.V., Koukos, P.I., Jim\u00e9nez-Garc\u00eda, B., Tsaregorodtsev, A., Verlato, M., Giachetti, A., Rosato, A., and Bonvin, A.M.J.J. (2021). Structural Biology in the Clouds: The WeNMR-EOSC Ecosystem. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.729513"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.abb.2004.08.014","article-title":"The Serine Acetyltransferase Reaction: Acetyl Transfer from an Acylpantothenyl Donor to an Alcohol","volume":"433","author":"Johnson","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/oxfordjournals.jbchem.a124469","article-title":"Enhancement of Serine-Sensitivity by a Gene Encoding Rhodanese-like Protein in Escherichia coli","volume":"115","author":"Hama","year":"1994","journal-title":"J. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1021\/bi0267893","article-title":"Random-Order Ternary Complex Reaction Mechanism of Serine Acetyltransferase from Escherichia coli","volume":"42","author":"Hindson","year":"2003","journal-title":"Biochemistry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3892\/ijmm.2013.1298","article-title":"Identification and Characterization of Serine Acetyltransferase Encoded by the Mycobacterium tuberculosis Rv2335 Gene","volume":"31","author":"Qiu","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.micpath.2019.04.002","article-title":"Characterization of Serine Acetyltransferase (CysE) from Methicillin-Resistant Staphylococcus aureus and Inhibitory Effect of Two Natural Products on CysE","volume":"131","author":"Chen","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8817","DOI":"10.1038\/s41598-017-09022-6","article-title":"Activation of an Anti-Bacterial Toxin by the Biosynthetic Enzyme CysK: Mechanism of Binding, Interaction Specificity and Competition with Cysteine Synthase","volume":"7","author":"Benoni","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1110\/ps.051492805","article-title":"Interaction of Serine Acetyltransferase with O-Acetylserine Sulfhydrylase Active Site: Evidence from Fluorescence Spectroscopy","volume":"14","author":"Campanini","year":"2005","journal-title":"Protein Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1021\/jm901325e","article-title":"Design of O-Acetylserine Sulfhydrylase Inhibitors by Mimicking Nature","volume":"53","author":"Salsi","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.bbapap.2012.09.009","article-title":"Fine Tuning of the Active Site Modulates Specificity in the Interaction of O-Acetylserine Sulfhydrylase Isozymes with Serine Acetyltransferase","volume":"1834","author":"Spyrakis","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA) Proteins Proteom."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1016\/S0021-9258(18)99657-2","article-title":"The Enzymic Synthesis of L-Cysteine in Escherichia coli and Salmonella typhimurium","volume":"241","author":"Kredich","year":"1966","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Magalh\u00e3es, J., Franko, N., Raboni, S., Annunziato, G., Tammela, P., Bruno, A., Bettati, S., Armao, S., Spadini, C., and Cabassi, C.S. (2021). Discovery of Substituted (2-Aminooxazol-4-Yl)Isoxazole-3-Carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants. Pharmaceuticals, 14.","DOI":"10.3390\/ph14020174"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1021\/acs.jmedchem.8b00147","article-title":"Nitro-Group-Containing Drugs","volume":"62","author":"Nepali","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Bisswanger, H. (2008). Enzyme Kinetics: Principles and Methods, Wiley-VCH. [2nd revised and updated ed.].","DOI":"10.1002\/9783527622023"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"E3095","DOI":"10.1073\/pnas.1500851112","article-title":"Accurate Secondary Structure Prediction and Fold Recognition for Circular Dichroism Spectroscopy","volume":"112","author":"Micsonai","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for Structure Building and Analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"ref_83","unstructured":"Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press. [2nd ed.]."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"O\u2019Gara, F., Dowling, D.N., and Boesten, B. (1994). Biocontrol of Root Diseases by Pseudomonas fluorescens CHA0: Current Concepts and Experimental Approaches. Molecular Ecology of Rhizosphere Microorganisms, VCH Weinheim.","DOI":"10.1002\/9783527615810"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1128\/jb.177.12.3606-3609.1995","article-title":"Anaerobic Activation of the Entire Denitrification Pathway in Pseudomonas aeruginosa Requires Anr, an Analog of Fnr","volume":"177","author":"Ye","year":"1995","journal-title":"J. Bacteriol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0147-619X(85)90068-X","article-title":"Plasmids Related to the Broad Host Range Vector, pRK290, Useful for Gene Cloning and for Monitoring Gene Expression","volume":"13","author":"Ditta","year":"1985","journal-title":"Plasmid"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1094\/MPMI.2000.13.2.232","article-title":"Small, Stable Shuttle Vectors Based on the Minimal pVS1 Replicon for Use in Gram-Negative, Plant-Associated Bacteria","volume":"13","author":"Heeb","year":"2000","journal-title":"Mol. Plant. Microbe Interact."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e00472-17","DOI":"10.1128\/JB.00472-17","article-title":"Ferric Uptake Regulator Fur Is Conditionally Essential in Pseudomonas aeruginosa","volume":"199","author":"Pasqua","year":"2017","journal-title":"J. Bacteriol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/jb.172.2.884-900.1990","article-title":"Identification and Characterization of Genes for a Second Anthranilate Synthase in Pseudomonas aeruginosa: Interchangeability of the Two Anthranilate Synthases and Evolutionary Implications","volume":"172","author":"Essar","year":"1990","journal-title":"J. Bacteriol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/mmi.14200","article-title":"Molecular Insights into the Master Regulator CysB-mediated Bacterial Virulence in Pseudomonas aeruginosa","volume":"111","author":"Song","year":"2019","journal-title":"Mol. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nchembio.186","article-title":"Absolute Metabolite Concentrations and Implied Enzyme Active Site Occupancy in Escherichia coli","volume":"5","author":"Bennett","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Smirnova, G., Tyulenev, A., Sutormina, L., Kalashnikova, T., Muzyka, N., Ushakov, V., Samoilova, Z., and Oktyabrsky, O. (2024). Regulation of Cysteine Homeostasis and Its Effect on Escherichia coli Sensitivity to Ciprofloxacin in LB Medium. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202403.1876.v1"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.bbapap.2015.02.013","article-title":"Moonlighting O-Acetylserine Sulfhydrylase: New Functions for an Old Protein","volume":"1854","author":"Campanini","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA) Proteins Proteom."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ijbiomac.2022.07.095","article-title":"Structural and Functional Studies of Serine Acetyltransferase Isoform from Entamoeba Histolytica Reveals Novel Role of the C-Terminal Tail in Loss of Regulation from Feedback Inhibition","volume":"217","author":"Dharavath","year":"2022","journal-title":"Int. J. Biol. Macromol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:44:36Z","timestamp":1780897476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":94,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27115091"],"URL":"https:\/\/doi.org\/10.3390\/ijms27115091","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]}}}