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Its natural metabolic versatility and extraordinary ability to degrade environmental pollutants (e.g., aromatic hydrocarbons such as benzene and toluene) enable it to thrive under various harsh environmental conditions. Constraint-based metabolic models constructed from genome sequences enable quantitative insight into the central and specialized metabolism within a target organism. These genome-scale models have been utilized to understand, optimize, and design new strategies for improved bioprocesses. Reduced modeling approaches have been used to elucidate<jats:italic>Nitrosomonas europaea<\/jats:italic>metabolism at a pathway level. However, genome-scale knowledge about the simultaneous oxidation of ammonia and pollutant metabolism of<jats:italic>N<\/jats:italic>.<jats:italic>europaea<\/jats:italic>remains limited. Here, we describe the reconstruction, manual curation, and validation of the genome-scale metabolic model for<jats:italic>N<\/jats:italic>.<jats:italic>europaea<\/jats:italic>,<jats:italic>i<\/jats:italic>GC535. This reconstruction is the most accurate metabolic model for a nitrifying organism to date, reaching an average prediction accuracy of over 90% under several growth conditions. The manually curated model can predict phenotypes under chemolithotrophic and chemolithoorganotrophic conditions while oxidating methane and wastewater pollutants. Calculated flux distributions under different trophic conditions show that several key pathways are affected by the type of carbon source available, including central carbon metabolism and energy production.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009828","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T18:42:35Z","timestamp":1643827355000},"page":"e1009828","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Flux balance analysis of the ammonia-oxidizing bacterium Nitrosomonas europaea ATCC19718 unravels specific metabolic activities while degrading toxic compounds"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6794-3917","authenticated-orcid":true,"given":"Gabriela","family":"Canto-Encalada","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8819-4150","authenticated-orcid":true,"given":"Diego","family":"Tec-Campos","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-8629","authenticated-orcid":true,"given":"Juan D.","family":"Tibocha-Bonilla","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-3296","authenticated-orcid":true,"given":"Karsten","family":"Zengler","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-5039","authenticated-orcid":true,"given":"Alejandro","family":"Zepeda","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-7429","authenticated-orcid":true,"given":"Cristal","family":"Zu\u00f1iga","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"pcbi.1009828.ref001","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.desal.2011.10.030","article-title":"Simulation of ammonia removal from industrial wastewater streams by means of a hollow-fiber membrane contactor.","volume":"285","author":"M Rezakazemi","year":"2012","journal-title":"Desalination"},{"issue":"8","key":"pcbi.1009828.ref002","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.watres.2006.02.012","article-title":"Kinetic and metabolic study of benzene, toluene and m-xylene in nitrifying batch cultures","volume":"40","author":"A Zepeda","year":"2006","journal-title":"Water Res"},{"issue":"1","key":"pcbi.1009828.ref003","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10532-016-9779-0","article-title":"Respirometric response and microbial succession of nitrifying sludge to m-cresol pulses in a sequencing batch reactor","volume":"28","author":"A Ordaz","year":"2017","journal-title":"Biodegradation"},{"issue":"10","key":"pcbi.1009828.ref004","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.chemosphere.2009.02.059","article-title":"p-Cresol biotransformation by a nitrifying consortium","volume":"75","author":"CD 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Fact"},{"issue":"1","key":"pcbi.1009828.ref025","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/1752-0509-5-163","article-title":"An experimentally-supported genome-scale metabolic network reconstruction for Yersinia pestis CO92","volume":"5","author":"P Charusanti","year":"2011","journal-title":"BMC Syst Biol"},{"issue":"3","key":"pcbi.1009828.ref026","doi-asserted-by":"crossref","first-page":"e1002980","DOI":"10.1371\/journal.pcbi.1002980","article-title":"The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum","volume":"9","author":"R Agren","year":"2013","journal-title":"PLoS Comput Biol."},{"issue":"3","key":"pcbi.1009828.ref027","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41596-018-0098-2","article-title":"Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0.","volume":"14","author":"L Heirendt","year":"2019","journal-title":"Nat Protoc."},{"issue":"2\u20133","key":"pcbi.1009828.ref028","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0005-2728(00)00171-7","article-title":"Electron transfer during the oxidation of ammonia by the chemolithotrophic bacterium Nitrosomonas europaea","volume":"1459","author":"M Whittaker","year":"2000","journal-title":"Biochim Biophys Acta\u2014Bioenerg"},{"issue":"7","key":"pcbi.1009828.ref029","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1007\/s00253-017-8092-0","article-title":"Regulation of membrane fixation and energy production\/conversion for adaptation and recovery of ZnO nanoparticle impacted Nitrosomonas europaea","volume":"101","author":"J Wu","year":"2017","journal-title":"Appl Microbiol Biotechnol"},{"issue":"6","key":"pcbi.1009828.ref030","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1128\/aem.60.6.1914-1920.1994","article-title":"Transformations of aromatic compounds by Nitrosomonas europaea","volume":"60","author":"WK Keener","year":"1994","journal-title":"Appl Environ Microbiol"},{"issue":"5","key":"pcbi.1009828.ref031","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1128\/aem.49.5.1101-1107.1985","article-title":"Test medium for the growth of Nitrosomonas europaea","volume":"49","author":"C Sato","year":"1985","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"pcbi.1009828.ref032","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1042\/bj2120031","article-title":"Methane oxidation by Nitrosomonas europaea","volume":"212","author":"MR Hyman","year":"1983","journal-title":"Biochem J"},{"issue":"1","key":"pcbi.1009828.ref033","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1128\/mr.53.1.68-84.1989","article-title":"Physiology, biochemistry, and specific inhibitors of CH4, NH4+, and CO oxidation by methanotrophs and nitrifiers","volume":"53","author":"C B\u00e9dard","year":"1989","journal-title":"Microbiol Rev"},{"issue":"2","key":"pcbi.1009828.ref034","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1128\/aem.45.2.401-410.1983","article-title":"Methane oxidation by Nitrosococcus oceanus and Nitrosomonas europaea","volume":"45","author":"RD Jones","year":"1983","journal-title":"Appl Environ Microbiol"},{"key":"pcbi.1009828.ref035","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-11-489","article-title":"Computationally efficient flux variability analysis","volume":"11","author":"S Gudmundsson","year":"2010","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"pcbi.1009828.ref036","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1104\/pp.93.1.40","article-title":"Isolation and characterization of the cytosolic and chloroplastic 3-phosphoglycerate kinase from spinach leaves","volume":"93","author":"E K\u00f6pke-Secundo","year":"1990","journal-title":"Plant Physiol"},{"issue":"2","key":"pcbi.1009828.ref037","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1104\/pp.93.2.374","article-title":"Separation, purification, and comparative properties of chloroplast and cytoplasmic phosphoglycerate kinase from barley leaves","volume":"93","author":"EM McMorrow","year":"1990","journal-title":"Plant Physiol"},{"issue":"2","key":"pcbi.1009828.ref038","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1104\/pp.55.2.168","article-title":"Chloroplast and Cytoplasmic Enzymes","volume":"55","author":"I Pacold","year":"1975","journal-title":"Plant Physiol"},{"issue":"7","key":"pcbi.1009828.ref039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0070396","article-title":"Functional Divergence and Convergent Evolution in the Plastid-Targeted Glyceraldehyde-3-Phosphate Dehydrogenases of Diverse Eukaryotic Algae.","volume":"8","author":"D Gaston","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"pcbi.1009828.ref040","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2307\/3869545","article-title":"Induction of malate synthase gene expression in senescent and detached organs of cucumber","volume":"4","author":"IA Graham","year":"1992","journal-title":"Plant Cell"},{"issue":"13","key":"pcbi.1009828.ref041","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1016\/j.watres.2013.04.052","article-title":"Inhibition of phenol on the rates of ammonia oxidation by Nitrosomonas europaea grown under batch, continuous fed, and biofilm conditions","volume":"47","author":"EG Lauchnor","year":"2013","journal-title":"Water Res"},{"issue":"7","key":"pcbi.1009828.ref042","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1021\/es3042912","article-title":"High-rate, high-yield production of methanol by ammonia-oxidizing bacteria","volume":"47","author":"E Taher","year":"2013","journal-title":"Environ Sci 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Schmidt","year":"2009","journal-title":"Curr Microbiol"},{"issue":"2","key":"pcbi.1009828.ref046","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1128\/br.41.2.419-448.1977","article-title":"Specialist phototrophs, lithotrophs, and methylotrophs: A unity among a diversity of procaryotes?","volume":"41","author":"AJ Smith","year":"1977","journal-title":"Bacteriol Rev"},{"key":"pcbi.1009828.ref047","volume-title":"Encyclopedia of Biological Chemistry","author":"A Adessi","year":"2013","edition":"2"},{"issue":"2","key":"pcbi.1009828.ref048","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1128\/jb.97.2.776-779.1969","article-title":"Biochemical basis of obligate autotrophy in Nitrosomonas europaea","volume":"97","author":"AB Hooper","year":"1969","journal-title":"J Bacteriol"},{"issue":"5","key":"pcbi.1009828.ref049","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s10482-013-9973-6","article-title":"L-Malate dehydrogenase activity in the reductive arm of the incomplete citric acid cycle of Nitrosomonas europaea","volume":"104","author":"CE Deutch","year":"2013","journal-title":"Antonie van Leeuwenhoek, Int J Gen Mol Microbiol."},{"key":"pcbi.1009828.ref050","volume-title":"Pub. Soc. Gen. Microbiol","author":"PM Wood","year":"1986"},{"issue":"1","key":"pcbi.1009828.ref051","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF00403501","article-title":"Regulation of autotrophic and heterotrophic metabolism in Pseudomonas oxalaticus OX1: Growth on mixtures of acetate and formate in continuous culture","volume":"123","author":"L Dijkhuizen","year":"1979","journal-title":"Arch Microbiol"},{"issue":"1","key":"pcbi.1009828.ref052","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nprot.2009.203","article-title":"A protocol for generating a high-quality genome-scale metabolic reconstruction","volume":"5","author":"I Thiele","year":"2010","journal-title":"Nat Protoc"},{"issue":"4","key":"pcbi.1009828.ref053","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jprot.2010.12.003","article-title":"Quantitative proteomic analysis of the chemolithoautotrophic bacterium Nitrosomonas europaea: Comparison of growing- and energy-starved cells","volume":"74","author":"MC Pellitteri-Hahn","year":"2011","journal-title":"J Proteomics"},{"key":"pcbi.1009828.ref054","doi-asserted-by":"crossref","DOI":"10.1007\/0-387-29298-5","volume-title":"Bergey\u2019s manual\u00ae of systematic bacteriology: volume two: The proteobacteria, part A introductory essays.","author":"DJ Brenner","year":"2005","edition":"2"},{"key":"pcbi.1009828.ref055","author":"CH Schilling","journal-title":"SimPhenyTM: A Computational Infrastructure for Systems Biology"},{"issue":"3","key":"pcbi.1009828.ref056","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nbt.1614","article-title":"What is flux balance?","volume":"28","author":"Jeffrey D. 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