Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow

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dc.contributor.authorBrunk, Elizabethko
dc.contributor.authorChang, Roger L.ko
dc.contributor.authorXia, Jingko
dc.contributor.authorHefzi, Hoomanko
dc.contributor.authorYurkovich, James T.ko
dc.contributor.authorKim, Donghyukko
dc.contributor.authorBuckmiller, Evanko
dc.contributor.authorWang, Harris H.ko
dc.contributor.authorCho, Byung-Kwanko
dc.contributor.authorYang, Chenko
dc.contributor.authorPalsson, Bernhard O.ko
dc.contributor.authorChurch, George M.ko
dc.contributor.authorLewis, Nathan E.ko
dc.date.accessioned2018-11-12T04:49:15Z-
dc.date.available2018-11-12T04:49:15Z-
dc.date.created2018-11-05-
dc.date.created2018-11-05-
dc.date.issued2018-10-
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.115, no.43, pp.11096 - 11101-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10203/246527-
dc.description.abstractUnderstanding the complex interactions of protein posttranslational modifications (PTMs) represents a major challenge in metabolic engineering, synthetic biology, and the biomedical sciences. Here, we present a workflow that integrates multiplex automated genome editing (MAGE), genome-scale metabolic modeling, and atomistic molecular dynamics to study the effects of PTMs on metabolic enzymes and microbial fitness. This workflow incorporates complementary approaches across scientific disciplines; provides molecular insight into how PTMs influence cellular fitness during nutrient shifts; and demonstrates how mechanistic details of PTMs can be explored at different biological scales. As a proof of concept, we present a global analysis of PTMs on enzymes in the metabolic network of Escherichia coll. Based on our workflow results, we conduct a more detailed, mechanistic analysis of the PTMs in three proteins: enolase, serine hydroxymethyltransferase, and transaldolase. Application of this workflow identified the roles of specific PTMs in observed experimental phenomena and demonstrated how individual PTMs regulate enzymes, pathways, and, ultimately, cell phenotypes.-
dc.languageEnglish-
dc.publisherNATL ACAD SCIENCES-
dc.subjectCONSTRAINT-BASED MODELS-
dc.subjectESCHERICHIA-COLI-
dc.subjectMICROBIAL-METABOLISM-
dc.subjectLYSINE ACETYLATION-
dc.subjectGENE-EXPRESSION-
dc.subjectAMBER-
dc.subjectPHOSPHOPROTEOME-
dc.subjectIDENTIFICATION-
dc.subjectTRANSALDOLASE-
dc.subjectADAPTATION-
dc.titleCharacterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow-
dc.typeArticle-
dc.identifier.wosid000448040500079-
dc.identifier.scopusid2-s2.0-85055596999-
dc.type.rimsART-
dc.citation.volume115-
dc.citation.issue43-
dc.citation.beginningpage11096-
dc.citation.endingpage11101-
dc.citation.publicationnamePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.identifier.doi10.1073/pnas.1811971115-
dc.contributor.localauthorCho, Byung-Kwan-
dc.contributor.nonIdAuthorBrunk, Elizabeth-
dc.contributor.nonIdAuthorChang, Roger L.-
dc.contributor.nonIdAuthorXia, Jing-
dc.contributor.nonIdAuthorHefzi, Hooman-
dc.contributor.nonIdAuthorYurkovich, James T.-
dc.contributor.nonIdAuthorKim, Donghyuk-
dc.contributor.nonIdAuthorBuckmiller, Evan-
dc.contributor.nonIdAuthorWang, Harris H.-
dc.contributor.nonIdAuthorYang, Chen-
dc.contributor.nonIdAuthorPalsson, Bernhard O.-
dc.contributor.nonIdAuthorChurch, George M.-
dc.contributor.nonIdAuthorLewis, Nathan E.-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorsystems biology-
dc.subject.keywordAuthorposttranslational modifications-
dc.subject.keywordAuthormetabolism-
dc.subject.keywordAuthorprotein chemistry-
dc.subject.keywordAuthoromics data-
dc.subject.keywordPlusCONSTRAINT-BASED MODELS-
dc.subject.keywordPlusESCHERICHIA-COLI-
dc.subject.keywordPlusMICROBIAL-METABOLISM-
dc.subject.keywordPlusLYSINE ACETYLATION-
dc.subject.keywordPlusGENE-EXPRESSION-
dc.subject.keywordPlusAMBER-
dc.subject.keywordPlusPHOSPHOPROTEOME-
dc.subject.keywordPlusIDENTIFICATION-
dc.subject.keywordPlusTRANSALDOLASE-
dc.subject.keywordPlusADAPTATION-
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