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dc.contributor.authorLi, Zhaopeng
dc.contributor.authorRinas, Ursula
dc.date.accessioned2020-10-08T13:23:53Z
dc.date.available2020-10-08T13:23:53Z
dc.date.issued2020-09-03
dc.identifier.citationBiotechnol Bioeng. 2020 Sep 3. doi: 10.1002/bit.27553. Epub ahead of print.en_US
dc.identifier.pmid32880889
dc.identifier.doi10.1002/bit.27553
dc.identifier.urihttp://hdl.handle.net/10033/622501
dc.description.abstractA comparison of the metabolic response of Escherichia coli BL21 (DE3) towards the production of human basic fibroblast growth factor (hFGF-2) or towards carbon overfeeding revealed similarities which point to constraints in anabolic pathways. Contrary to expectations, neither energy generation (e.g., ATP) nor provision of precursor molecules for nucleotides (e.g., uracil) and amino acids (e.g., pyruvate, glutamate) limit host cell and plasmid-encoded functions. Growth inhibition is assumed to occur when hampered anabolic capacities do not match with the ongoing and overwhelming carbon catabolism. Excessive carbon uptake leads to by-product secretion, for example, pyruvate, acetate, glutamate, and energy spillage, for example, accumulation and degradation of adenine nucleotides with concomitant accumulation of extracellular hypoxanthine. The cellular response towards compromised anabolic capacities involves downregulation of cAMP formation, presumably responsible for subsequently better-controlled glucose uptake and resultant accumulation of glucose in the culture medium. Growth inhibition is neglectable under conditions of reduced carbon availability when hampered anabolic capacities also match with catabolic carbon processing. The growth inhibitory effect with accompanying energy spillage, respectively, hypoxanthine secretion and cessation of cAMP formation is not unique to the production of hFGF-2 but observed during the production of other proteins and also during overexpression of genes without transcript translation.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectEscherichia colien_US
dc.subjectcarbon overfeeding responseen_US
dc.subjectenergy spilling and hypoxanthine secretionen_US
dc.subjectrecombinant protein production-associated metabolic burdenen_US
dc.titleRecombinant protein production-associated metabolic burden reflects anabolic constraints and reveals similarities to a carbon overfeeding response.en_US
dc.typeArticleen_US
dc.identifier.eissn1097-0290
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalBiotechnology and bioengineeringen_US
refterms.dateFOA2020-10-08T13:23:54Z
dc.source.journaltitleBiotechnology and bioengineering
dc.source.countryUnited States


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