{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:18:27Z","timestamp":1791123507209,"version":"4.1.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,2,15]],"date-time":"2013-02-15T00:00:00Z","timestamp":1360886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We previously demonstrated efficient<jats:sc>l<\/jats:sc>-valine production by metabolically engineered<jats:named-content content-type=\"genus-species\">Corynebacterium glutamicum<\/jats:named-content>under oxygen deprivation. To achieve the high productivity, a NADH\/NADPH cofactor imbalance during the synthesis of<jats:sc>l<\/jats:sc>-valine was overcome by engineering NAD-preferring mutant acetohydroxy acid isomeroreductase (AHAIR) and using NAD-specific leucine dehydrogenase from<jats:named-content content-type=\"genus-species\">Lysinibacillus sphaericus<\/jats:named-content>. Lactate as a by-product was largely eliminated by disrupting the lactate dehydrogenase gene<jats:italic>ldhA<\/jats:italic>. Nonetheless, a few other by-products, particularly succinate, were still produced and acted to suppress the<jats:sc>l<\/jats:sc>-valine yield. Eliminating these by-products therefore was deemed key to improving the<jats:sc>l<\/jats:sc>-valine yield. By additionally disrupting the phosphoenolpyruvate carboxylase gene<jats:italic>ppc<\/jats:italic>, succinate production was effectively suppressed, but both glucose consumption and<jats:sc>l<\/jats:sc>-valine production dropped considerably due to the severely elevated intracellular NADH\/NAD<jats:sup>+<\/jats:sup>ratio. In contrast, this perturbed intracellular redox state was more than compensated for by deletion of three genes associated with NADH-producing acetate synthesis and overexpression of five glycolytic genes, including<jats:italic>gapA<\/jats:italic>, encoding NADH-inhibited glyceraldehyde-3-phosphate dehydrogenase. Inserting feedback-resistant mutant acetohydroxy acid synthase and NAD-preferring mutant AHAIR in the chromosome resulted in higher<jats:sc>l<\/jats:sc>-valine yield and productivity. Deleting the alanine transaminase gene<jats:italic>avtA<\/jats:italic>suppressed alanine production. The resultant strain produced 1,280 mM<jats:sc>l<\/jats:sc>-valine at a yield of 88% mol mol of glucose<jats:sup>\u22121<\/jats:sup>after 24 h under oxygen deprivation, a vastly improved yield over our previous best.<\/jats:p>","DOI":"10.1128\/aem.02806-12","type":"journal-article","created":{"date-parts":[[2012,12,16]],"date-time":"2012-12-16T01:45:28Z","timestamp":1355622328000},"page":"1250-1257","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":114,"title":["Engineering of Corynebacterium glutamicum for High-Yield<scp>l<\/scp>-Valine Production under Oxygen Deprivation Conditions"],"prefix":"10.1128","volume":"79","author":[{"given":"Satoshi","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Suda","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimio","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Natsuma","sequence":"additional","affiliation":[{"name":"Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Hiraga","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Jojima","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Inui","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Yukawa","sequence":"additional","affiliation":[{"name":"Research Institute of Innovative Technology for the Earth, Kizugawadai, Kizugawa, Kyoto, Japan"},{"name":"Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702609104"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-009-2307-y"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1656(03)00149-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-008-1444-z"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200700168"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06450"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02972-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2011.02.004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1656(03)00162-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.1.207-213.2005"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb01474.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.22.7639-7646.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01025-08"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00575-11"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/btpr.345","article-title":"Importance of NADPH supply for improved L-valine formation in Corynebacterium glutamicum","volume":"26","author":"Bartek T","year":"2010","unstructured":"BartekT BlombachB Z\u00f6nnchenE MakusP LangS EikmannsBJ OldigesM. 2010. 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