{"9ce34124eaffe2a799aade38deec413dbastian":{"DOI":"10.1186/s12934-015-0362-x","ISBN":"","ISSN":"1475-2859","URL":"","abstract":"BACKGROUND: 2,3-Butanediol is an important bulk chemical with a wide range of applications. In bacteria, this metabolite is synthesised from pyruvate via a three-step pathway involving α-acetolactate synthase, α-acetolactate decarboxylase and 2,3-butanediol dehydrogenase. Thus far, the best producers of 2,3-butanediol are pathogenic strains, hence, the development of more suitable organisms for industrial scale fermentation is needed. Herein, 2,3-butanediol production was engineered in the Generally Regarded As Safe (GRAS) organism Corynebacterium glutamicum. A two-stage fermentation process was implemented: first, cells were grown aerobically on acetate; in the subsequent production stage cells were used to convert glucose into 2,3-butanediol under non-growing and oxygen-limiting conditions.\nRESULTS: A gene cluster, encoding the 2,3-butanediol biosynthetic pathway of Lactococcus lactis, was assembled and expressed in background strains, C. glutamicum ΔldhA, C. glutamicum ΔaceEΔpqoΔldhA and C. glutamicum ΔaceEΔpqoΔldhAΔmdh, tailored to minimize pyruvate-consuming reactions, i.e., to prevent carbon loss in lactic, acetic and succinic acids. Producer strains were characterized in terms of activity of the relevant enzymes in the 2,3-butanediol forming pathway, growth, and production of 2,3-butanediol under oxygen-limited conditions. Productivity was maximized by manipulating the aeration rate in the production phase. The final strain, C. glutamicum ΔaceEΔpqoΔldhAΔmdh(pEKEx2-als,aldB,Ptuf butA), under optimized conditions produced 2,3-butanediol with a 0.66 mol mol(-1) yield on glucose, an overall productivity of 0.2 g L(-1) h(-1) and a titer of 6.3 g L(-1).\nCONCLUSIONS: We have successfully developed C. glutamicum into an efficient cell factory for 2,3-butanediol production. The use of the engineered strains as a basis for production of acetoin, a widespread food flavour, is proposed.","annote":"","author":[{"family":"Radoš","given":"Dušica"},{"family":"Carvalho","given":"Ana Lúcia"},{"family":"Wieschalka","given":"Stefan"},{"family":"Neves","given":"Ana Rute"},{"family":"Blombach","given":"Bastian"},{"family":"Eikmanns","given":"Bernhard J."},{"family":"Santos","given":"Helena"}],"citation-label":"rados_engineering_2015","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Microb. Cell Fact.","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2015","oct"]],"literal":"2015"},"event-place":"","id":"9ce34124eaffe2a799aade38deec413dbastian","interhash":"518ec5750d920964df1a659788edff11","intrahash":"9ce34124eaffe2a799aade38deec413d","issue":"","issued":{"date-parts":[["2015","oct"]],"literal":"2015"},"keyword":"Bacterial Bioreactors, Butylene Complex, Corynebacterium Dehydrogenase Dehydrogenase, Engineering Family, Glucose, Glycols, L-Lactate Lactococcus Metabolic Multigene Oxygen, Proteins, Pyruvate glutamicum, lactis, myown","misc":{"pmid":"26511723","issn":"1475-2859","pmcid":"PMC4625470","language":"eng","doi":"10.1186/s12934-015-0362-x"},"note":"","number":"","page":"171","page-first":"171","publisher":"","publisher-place":"","status":"","title":"Engineering Corynebacterium glutamicum for the production of 2,3-butanediol","type":"article-journal","username":"bastian","version":"","volume":"14"}}