An Engineered Escherichia coli Strain with Synthetic Metabolism for in‐Cell Production of Translationally Active Methionine Derivatives

dc.contributor.authorSchipp, Christian Johannes
dc.contributor.authorMa, Ying
dc.contributor.authorAl‐Shameri, Ammar
dc.contributor.authorD'Alessio, Federico
dc.contributor.authorNeubauer, Peter
dc.contributor.authorContestabile, Roberto
dc.contributor.authorBudisa, Nediljko
dc.contributor.authordi Salvo, Martino Luigi
dc.date.accessioned2021-02-25T11:36:31Z
dc.date.available2021-02-25T11:36:31Z
dc.date.issued2020-10-13
dc.date.updated2021-02-22T12:53:17Z
dc.description.abstractIn the last decades, it has become clear that the canonical amino acid repertoire codified by the universal genetic code is not up to the needs of emerging biotechnologies. For this reason, extensive genetic code re‐engineering is essential to expand the scope of ribosomal protein translation, leading to reprogrammed microbial cells equipped with an alternative biochemical alphabet to be exploited as potential factories for biotechnological purposes. The prerequisite for this to happen is a continuous intracellular supply of noncanonical amino acids through synthetic metabolism from simple and cheap precursors. We have engineered an Escherichia coli bacterial system that fulfills these requirements through reconfiguration of the methionine biosynthetic pathway and the introduction of an exogenous direct trans‐sulfuration pathway. Our metabolic scheme operates in vivo, rescuing intermediates from core cell metabolism and combining them with small bio‐orthogonal compounds. Our reprogrammed E. coli strain is capable of the in‐cell production of l‐azidohomoalanine, which is directly incorporated into proteins in response to methionine codons. We thereby constructed a prototype suitable for economic, versatile, green sustainable chemistry, pushing towards enzyme chemistry and biotechnology‐based production.en
dc.description.sponsorshipTU Berlin, Open-Access-Mittel – 2020en
dc.description.sponsorshipDFG, 53182490, EXC 314: Unifying Concepts in Catalysisen
dc.identifier.eissn1439-7633
dc.identifier.issn1439-4227
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/12678
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-11476
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftende
dc.subject.otherclick chemistryen
dc.subject.othergenetic code expansionen
dc.subject.othergreen chemistryen
dc.subject.othermetabolic engineeringen
dc.subject.othernoncanonical amino acidsen
dc.subject.othertrans-sulfurationen
dc.titleAn Engineered Escherichia coli Strain with Synthetic Metabolism for in‐Cell Production of Translationally Active Methionine Derivativesen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.doi10.1002/cbic.202000257en
dcterms.bibliographicCitation.issue24en
dcterms.bibliographicCitation.journaltitleChemBioChemen
dcterms.bibliographicCitation.originalpublishernameWileyen
dcterms.bibliographicCitation.originalpublisherplaceNew York, NYen
dcterms.bibliographicCitation.pageend3538en
dcterms.bibliographicCitation.pagestart3525en
dcterms.bibliographicCitation.volume21en
tub.accessrights.dnbfreeen
tub.affiliationFak. 2 Mathematik und Naturwissenschaften::Inst. Chemie::FG Biokatalysede
tub.affiliation.facultyFak. 2 Mathematik und Naturwissenschaftende
tub.affiliation.groupFG Biokatalysede
tub.affiliation.instituteInst. Chemiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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