{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:51:19Z","timestamp":1791535879523,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32000037"],"award-info":[{"award-number":["32000037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tryptophan, an essential aromatic amino acid, is widely used in animal feed, food additives, and pharmaceuticals. Although sustainable and environmentally friendly, microbial tryptophan production from renewable feedstocks is limited by low biosynthesis and transport rates. Here, an <jats:italic>Escherichia coli<\/jats:italic> strain capable of efficient tryptophan production was generated by improving and balancing the supply of precursors and by engineering membrane transporters. Tryptophan biosynthesis was increased by eliminating negative regulatory factors, blocking competing pathways, and preventing tryptophan degradation. Promoter engineering balanced the supply of the precursors erythrose\u20104\u2010phosphate and phosphoenolpyruvate, as well as the availability of serine. Finally, the engineering of tryptophan transporters prevented feedback inhibition and growth toxicity. Fed\u2010batch fermentation of the final strain (TRP12) in a 5\u2009L bioreactor produced 52.1\u2009g\u00b7L<jats:sup>\u22121<\/jats:sup> of tryptophan, with a yield of 0.171\u2009g\u00b7g<jats:sup>\u22121<\/jats:sup> glucose and productivity of 1.45\u2009g\u00b7L<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>. The metabolic engineering strategy described here paves the way for high\u2010performance microbial cell factories aimed at the production of tryptophan as well as other valuable chemicals.<\/jats:p>","DOI":"10.1002\/bit.28019","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:51:49Z","timestamp":1640170309000},"page":"983-993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Enhancing tryptophan production by balancing precursors in <i>Escherichia coli<\/i>"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-3438","authenticated-orcid":false,"given":"Liang","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guipeng","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Song","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-3860","authenticated-orcid":false,"given":"Xiulai","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology Jiangnan University  Wuxi China"},{"name":"International Joint Laboratory on Food Safety Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191652"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00205035"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2018.05.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26906"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-018-2020-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2020.07.003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2017.12.026"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/13102818.2019.1674692"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-015-0192-x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11793-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2019.07.005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41929-019-0411-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26580"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-019-1090-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2016.10.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2016.10.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0893-921"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41929-018-0212-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2020.107548"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2012.02.088"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2007.02.034"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-018-2106-5"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2017.05.006"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1226"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2018.04.008"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/605219"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2019.10.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26834"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-013-5026-3"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2019.07.011"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27665"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2425"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2019.11.007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2018.04.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-011-0978-8"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2011.11.009"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bit.28019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:51:46Z","timestamp":1760046706000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.28019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,30]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/bit.28019"],"URL":"https:\/\/doi.org\/10.1002\/bit.28019","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,30]]},"assertion":[{"value":"2021-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}