{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:24:55Z","timestamp":1792077895631,"version":"4.4.0"},"reference-count":75,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T00:00:00Z","timestamp":1713657600000},"content-version":"am","delay-in-days":356,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Metabolic Engineering"],"published-print":{"date-parts":[[2023,5]]},"DOI":"10.1016\/j.ymben.2023.03.011","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T17:57:07Z","timestamp":1680717427000},"page":"231-241","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Silk fibroin production in Escherichia coli is limited by a positive feedback loop between metabolic burden and toxicity stress"],"prefix":"10.1016","volume":"77","author":[{"given":"Zhengyang","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Worland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjie J.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Helen","family":"Zha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1405-0565","authenticated-orcid":false,"given":"Mattheos","family":"Koffas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymben.2023.03.011_bib1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ymben.2019.04.010","article-title":"Cyanobacterial carboxysome mutant analysis reveals the influence of enzyme compartmentalization on cellular metabolism and metabolic network rigidity","volume":"54","author":"Abernathy","year":"2019","journal-title":"Metab. Eng."},{"key":"10.1016\/j.ymben.2023.03.011_bib2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0142-9612(02)00353-8","article-title":"Silk-based biomaterials","volume":"24","author":"Altman","year":"2003","journal-title":"Biomaterials"},{"key":"10.1016\/j.ymben.2023.03.011_bib3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nchembio.2269","article-title":"Biomimetic spinning of artificial spider silk from a chimeric minispidroin","volume":"13","author":"Andersson","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib4","first-page":"e3583","article-title":"Metabolic pathway confirmation and discovery through 13C-labeling of proteinogenic amino acids","author":"Au - You","year":"2012","journal-title":"JoVE"},{"key":"10.1016\/j.ymben.2023.03.011_bib5","doi-asserted-by":"crossref","first-page":"7054","DOI":"10.1038\/s41467-022-34647-1","article-title":"Feedforward growth rate control mitigates gene activation burden","volume":"13","author":"Barajas","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymben.2023.03.011_bib6","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1021\/acs.biomac.8b00980","article-title":"Recombinant spidroins fully replicate primary mechanical properties of natural spider silk","volume":"19","author":"Bowen","year":"2018","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.ymben.2023.03.011_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.btre.2020.e00441","article-title":"Cost analysis based on bioreactor cultivation conditions: production of a soluble recombinant protein using Escherichia coli BL21 (DE3)","volume":"26","author":"Cardoso","year":"2020","journal-title":"Biotechnology Reports"},{"key":"10.1016\/j.ymben.2023.03.011_bib8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1475-2859-12-21","article-title":"Batch production of a silk-elastin-like protein in E. coli BL21(DE3): key parameters for optimisation","volume":"12","author":"Collins","year":"2013","journal-title":"Microb. Cell Factories"},{"key":"10.1016\/j.ymben.2023.03.011_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.mec.2023.e00219","article-title":"Novel insights into construct toxicity, strain optimization, and primary sequence design for producing recombinant silk fibroin and elastin-like peptide in E. coli","author":"Connor","year":"2023","journal-title":"Metabolic Engineering Communications"},{"key":"10.1016\/j.ymben.2023.03.011_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2020.100854","article-title":"Application of stable isotope tracing to elucidate metabolic dynamics during yarrowia lipolytica \u03b1-ionone fermentation","volume":"23","author":"Czajka","year":"2020","journal-title":"iScience"},{"key":"10.1016\/j.ymben.2023.03.011_bib11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/2193-1801-2-322","article-title":"Non-conventional induction strategies for production of subunit swine erysipelas vaccine antigen in rE. coli fed-batch cultures","volume":"2","author":"da Silva","year":"2013","journal-title":"SpringerPlus"},{"key":"10.1016\/j.ymben.2023.03.011_bib12","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2016.0380","article-title":"Control theory meets synthetic biology","volume":"13","author":"Del Vecchio","year":"2016","journal-title":"J. R. Soc. Interface"},{"key":"10.1016\/j.ymben.2023.03.011_bib13","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1752-0509-7-74","article-title":"COBRApy: COnstraints-based reconstruction and analysis for Python","volume":"7","author":"Ebrahim","year":"2013","journal-title":"BMC Syst. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib14","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.tibtech.2006.09.001","article-title":"Overcoming acetate in Escherichia coli recombinant protein fermentations","volume":"24","author":"Eiteman","year":"2006","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib15","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ng1555","article-title":"Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism","volume":"37","author":"Fischer","year":"2005","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymben.2023.03.011_bib16","doi-asserted-by":"crossref","first-page":"10039","DOI":"10.1073\/pnas.1215283110","article-title":"Glycolytic strategy as a tradeoff between energy yield and protein cost","volume":"110","author":"Flamholz","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymben.2023.03.011_bib17","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1126\/science.1057561","article-title":"Extreme diversity, conservation, and convergence of spider silk fibroin sequences","volume":"291","author":"Gatesy","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.ymben.2023.03.011_bib18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0734-9750(95)00004-A","article-title":"Metabolic load and heterologous gene expression","volume":"13","author":"Glick","year":"1995","journal-title":"Biotechnol. Adv."},{"key":"10.1016\/j.ymben.2023.03.011_bib19","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1242\/jeb.202.23.3295","article-title":"The mechanical design of spider silks: from fibroin sequence to mechanical function","volume":"202","author":"Gosline","year":"1999","journal-title":"J. Exp. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib20","article-title":"EColiCore2: a reference network model of the central metabolism of Escherichia coli and relationships to its genome-scale parent model","volume":"7","author":"H\u00e4dicke","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymben.2023.03.011_bib21","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1016\/j.polymer.2008.08.006","article-title":"Polymeric materials based on silk proteins","volume":"49","author":"Hardy","year":"2008","journal-title":"Polymer"},{"key":"10.1016\/j.ymben.2023.03.011_bib22","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1186\/s12859-016-1314-0","article-title":"WUFlux: an open-source platform for 13C metabolic flux analysis of bacterial metabolism","volume":"17","author":"He","year":"2016","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.ymben.2023.03.011_bib23","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/bit.25124","article-title":"Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C-metabolic flux analysis","volume":"111","author":"He","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2023.03.011_bib24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ymben.2016.12.008","article-title":"Deciphering flux adjustments of engineered E. coli cells during fermentation with changing growth conditions","volume":"39","author":"He","year":"2017","journal-title":"Metab. Eng."},{"key":"10.1016\/j.ymben.2023.03.011_bib25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jbiotec.2011.06.016","article-title":"Quantification of metabolic limitations during recombinant protein production in Escherichia coli","volume":"155","author":"Heyland","year":"2011","journal-title":"J. Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/b93994","article-title":"Stress induced by recombinant protein production in Escherichia coli","author":"Hoffmann","year":"2004","journal-title":"Physiological stress responses in bioprocesses"},{"key":"10.1016\/j.ymben.2023.03.011_bib27","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.201800465","article-title":"The biomedical use of silk: past, present, future","volume":"8","author":"Holland","year":"2019","journal-title":"Advanced healthcare materials"},{"key":"10.1016\/j.ymben.2023.03.011_bib28","series-title":"Microbial Metabolic Engineering: Methods and Protocols","first-page":"215","article-title":"13C-Fingerprinting and metabolic flux analysis of bacterial metabolisms","author":"Hollinshead","year":"2019"},{"key":"10.1016\/j.ymben.2023.03.011_bib29","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s13068-016-0630-y","article-title":"Examining Escherichia coli glycolytic pathways, catabolite repression, and metabolite channeling using \u0394pfk mutants","volume":"9","author":"Hollinshead","year":"2016","journal-title":"Biotechnol. Biofuels"},{"key":"10.1016\/j.ymben.2023.03.011_bib30","doi-asserted-by":"crossref","first-page":"17498","DOI":"10.1074\/jbc.M109.095570","article-title":"Metabolic and transcriptional response to cofactor perturbations in Escherichia coli","volume":"285","author":"Holm","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymben.2023.03.011_bib31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1109\/MCS.2018.2810459","article-title":"Control theory for synthetic biology: recent advances in system characterization, control design, and controller implementation for synthetic biology","volume":"38","author":"Hsiao","year":"2018","journal-title":"IEEE Control Syst. Mag."},{"key":"10.1016\/j.ymben.2023.03.011_bib32","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/biot.201500412","article-title":"Functionalized silk assembled from a recombinant spider silk fusion protein (Z\u20104RepCT) produced in the methylotrophic yeast Pichia pastoris","volume":"11","author":"Jansson","year":"2016","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2023.03.011_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/bit.260360102","article-title":"Production of recombinant human growth hormone in Escherichia coli: expression of different precursors and physiological effects of glucose, acetate, and salts","volume":"36","author":"Jensen","year":"1990","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2023.03.011_bib34","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ymben.2022.01.009","article-title":"Secretory production of spider silk proteins in metabolically engineered Corynebacterium glutamicum for spinning into tough fibers","volume":"70","author":"Jin","year":"2022","journal-title":"Metab. Eng."},{"key":"10.1016\/j.ymben.2023.03.011_bib35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/biot.201200267","article-title":"Metabolic costs of amino acid and protein production in Escherichia coli","volume":"8","author":"Kaleta","year":"2013","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2023.03.011_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioeco.2022.100033","article-title":"Navigating the Valley of death: perceptions of industry and academia on production platforms and opportunities in biotechnology","volume":"2","author":"Kampers","year":"2022","journal-title":"EFB Bioeconomy Journal"},{"key":"10.1016\/j.ymben.2023.03.011_bib37","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1099\/mic.0.27481-0","article-title":"Metabolic flux analysis of Escherichia coli in glucose-limited continuous culture. I. Growth-rate-dependent metabolic efficiency at steady state","volume":"151","author":"Kayser","year":"2005","journal-title":"Microbiology"},{"key":"10.1016\/j.ymben.2023.03.011_bib38","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1128\/JB.184.14.3909-3916.2002","article-title":"The glycolytic flux in Escherichia coli is controlled by the demand for ATP","volume":"184","author":"Koebmann","year":"2002","journal-title":"J. Bacteriol."},{"key":"10.1016\/j.ymben.2023.03.011_bib39","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1002\/bit.27371","article-title":"Amino acid supplementation for enhancing recombinant protein production in E. coli","volume":"117","author":"Kumar","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2023.03.011_bib40","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1126\/science.1065780","article-title":"Spider silk fibers spun from soluble recombinant silk produced in mammalian cells","volume":"295","author":"Lazaris","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.ymben.2023.03.011_bib41","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1128\/aem.56.4.1004-1011.1990","article-title":"Comparison of growth, acetate production, and acetate inhibition of Escherichia coli strains in batch and fed-batch fermentations","volume":"56","author":"Luli","year":"1990","journal-title":"Appl. Environ. Microbiol."},{"key":"10.1016\/j.ymben.2023.03.011_bib42","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1021\/acssynbio.7b00172","article-title":"Fundamental design principles for transcription-factor-based metabolite biosensors","volume":"6","author":"Mannan","year":"2017","journal-title":"ACS Synth. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep25263","article-title":"Silk fibroin as edible coating for perishable food preservation","volume":"6","author":"Marelli","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymben.2023.03.011_bib44","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.63661","article-title":"Control and regulation of acetate overflow in Escherichia coli","volume":"10","author":"Millard","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.ymben.2023.03.011_bib45","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/1521-3935(200207)203:10\/11<1658::AID-MACP1658>3.0.CO;2-3","article-title":"Regenerated silk fibroin films: thermal and dynamic mechanical analysis","volume":"203","author":"Motta","year":"2002","journal-title":"Macromol. Chem. Phys."},{"key":"10.1016\/j.ymben.2023.03.011_bib46","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.cell.2015.05.019","article-title":"Using genome-scale models to predict biological capabilities","volume":"161","author":"O'Brien","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymben.2023.03.011_bib47","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bej.2004.09.012","article-title":"Metabolic flux analysis of recombinant protein overproduction in Escherichia coli","volume":"22","author":"\u00d6zkan","year":"2005","journal-title":"Biochem. Eng. J."},{"key":"10.1016\/j.ymben.2023.03.011_bib48","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nchembio.2077","article-title":"Metabolite concentrations, fluxes and free energies imply efficient enzyme usage","volume":"12","author":"Park","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib49","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/s41587-019-0171-6","article-title":"Overcoming genetic heterogeneity in industrial fermentations","volume":"37","author":"Rugbjerg","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1752-0509-4-122","article-title":"A systematic investigation of Escherichia coli central carbon metabolism in response to superoxide stress","volume":"4","author":"Rui","year":"2010","journal-title":"BMC Syst. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1752-0509-8-67","article-title":"Source and regulation of flux variability in Escherichia coli","volume":"8","author":"San Rom\u00e1n","year":"2014","journal-title":"BMC Syst. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib52","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.3390\/ma12244086","article-title":"Chemical synthesis of silk-mimetic polymers","volume":"12","author":"Sarkar","year":"2019","journal-title":"Materials"},{"key":"10.1016\/j.ymben.2023.03.011_bib53","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1023\/B:TRAG.0000017175.78809.7a","article-title":"Purification of spider silk-elastin from transgenic plants and application for human chondrocyte proliferation","volume":"13","author":"Scheller","year":"2004","journal-title":"Transgenic Res."},{"key":"10.1016\/j.ymben.2023.03.011_bib54","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mattod.2021.07.020","article-title":"High-yield production of a super-soluble miniature spidroin for biomimetic high-performance materials","volume":"50","author":"Schmuck","year":"2021","journal-title":"Mater. Today"},{"key":"10.1016\/j.ymben.2023.03.011_bib55","series-title":"Bioprocess Engineering: Basic Concepts","author":"Shuler","year":"2002"},{"key":"10.1016\/j.ymben.2023.03.011_bib56","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003658","article-title":"Optimizing metabolite production using periodic oscillations","volume":"10","author":"Sowa","year":"2014","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.ymben.2023.03.011_bib57","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/0167-7799(93)90099-U","article-title":"Metabolic engineering\u2014methodologies and future prospects","volume":"11","author":"Stephanopoulos","year":"1993","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib58","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1126\/science.1904627","article-title":"Network rigidity and metabolic engineering in metabolite overproduction","volume":"252","author":"Stephanopoulos","year":"1991","journal-title":"Science"},{"key":"10.1016\/j.ymben.2023.03.011_bib59","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0032-9592(00)00140-0","article-title":"Acetic acid accumulation in aerobic growth of recombinant Escherichia coli","volume":"35","author":"Suarez","year":"2000","journal-title":"Process Biochemistry"},{"key":"10.1016\/j.ymben.2023.03.011_bib60","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1126\/science.1188308","article-title":"Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells","volume":"329","author":"Taniguchi","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.ymben.2023.03.011_bib61","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nprot.2008.250","article-title":"A protocol for the production of recombinant spider silk-like proteins for artificial fiber spinning","volume":"4","author":"Teul\u00e9","year":"2009","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ymben.2023.03.011_bib62","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.actbio.2013.08.020","article-title":"Structure\u2013function\u2013property\u2013design interplay in biopolymers: spider silk","volume":"10","author":"Tokareva","year":"2014","journal-title":"Acta Biomater."},{"key":"10.1016\/j.ymben.2023.03.011_bib63","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/1751-7915.12081","article-title":"Recombinant DNA production of spider silk proteins","volume":"6","author":"Tokareva","year":"2013","journal-title":"Microb. Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib64","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/adfm.200902050","article-title":"Functionalized\u2010silk\u2010based active optofluidic devices","volume":"20","author":"Tsioris","year":"2010","journal-title":"Adv. Funct. Mater."},{"key":"10.1016\/j.ymben.2023.03.011_bib65","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.progpolymsci.2007.05.013","article-title":"Silk as a biomaterial","volume":"32","author":"Vepari","year":"2007","journal-title":"Prog. Polym. Sci."},{"key":"10.1016\/j.ymben.2023.03.011_bib66","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/bit.10380","article-title":"Metabolic adaptation of Escherichia coli during temperature\u2010induced recombinant protein production: 2. Redirection of metabolic fluxes","volume":"80","author":"Weber","year":"2002","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2023.03.011_bib67","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s11033-009-9615-2","article-title":"Transgenic silkworms (Bombyx mori) produce recombinant spider dragline silk in cocoons","volume":"37","author":"Wen","year":"2010","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.ymben.2023.03.011_bib68","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.tibtech.2020.09.007","article-title":"Host systems for the production of recombinant spider silk","volume":"39","author":"Whittall","year":"2021","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib69","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.tibtech.2016.02.010","article-title":"Metabolic burden: cornerstones in synthetic biology and metabolic engineering applications","volume":"34","author":"Wu","year":"2016","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib70","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/mben.1998.0103","article-title":"Metabolic flux analysis ofEscherichia coliDeficient in the acetate production pathway and expressing theBacillus subtilisAcetolactate synthase","volume":"1","author":"Yang","year":"1999","journal-title":"Metab. Eng."},{"key":"10.1016\/j.ymben.2023.03.011_bib71","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.procbio.2016.01.006","article-title":"Hyper-production of large proteins of spider dragline silk MaSp2 by Escherichia coli via synthetic biology approach","volume":"51","author":"Yang","year":"2016","journal-title":"Process Biochemistry"},{"key":"10.1016\/j.ymben.2023.03.011_bib72","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ab.2014.12.005","article-title":"Using photosystem I as a reporter protein for 13C analysis in a coculture containing cyanobacterium and a heterotrophic bacterium","volume":"477","author":"You","year":"2015","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ymben.2023.03.011_bib73","article-title":"Metabolic pathway confirmation and discovery through (13)C-labeling of proteinogenic amino acids","volume":"e3583","author":"You","year":"2012","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.ymben.2023.03.011_bib74","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.copbio.2014.10.004","article-title":"13C metabolic flux analysis of recombinant expression hosts","volume":"30","author":"Young","year":"2014","journal-title":"Curr. Opin. Biotechnol."},{"key":"10.1016\/j.ymben.2023.03.011_bib75","doi-asserted-by":"crossref","first-page":"7797","DOI":"10.1128\/AEM.05676-11","article-title":"Selective utilization of exogenous amino acids by Dehalococcoides ethenogenes strain 195 and its effects on growth and dechlorination activity","volume":"77","author":"Zhuang","year":"2011","journal-title":"Appl. Environ. Microbiol."}],"container-title":["Metabolic Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717623000514?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717623000514?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T23:15:46Z","timestamp":1761088546000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096717623000514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":75,"alternative-id":["S1096717623000514"],"URL":"https:\/\/doi.org\/10.1016\/j.ymben.2023.03.011","relation":{},"ISSN":["1096-7176"],"issn-type":[{"value":"1096-7176","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Silk fibroin production in Escherichia coli is limited by a positive feedback loop between metabolic burden and toxicity stress","name":"articletitle","label":"Article Title"},{"value":"Metabolic Engineering","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymben.2023.03.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}