PUMA publications for /tag/glutamicum,%20Metabolic%20andhttps://puma.ub.uni-stuttgart.de/tag/glutamicum,%20Metabolic%20andPUMA RSS feed for /tag/glutamicum,%20Metabolic%20and2024-03-28T11:15:55+01:00Importance of NADPH supply for improved L-valine formation in Corynebacterium glutamicumhttps://puma.ub.uni-stuttgart.de/bibtex/2dfb0ffb355b1bb961e53e70b66a327fd/bastianbastian2018-02-09T13:18:17+01:00Biological, Cell Corynebacterium Culture Fermentation, Glucose-6-Phosphate Isomerase, Media, Metabolic Metabolome Models, NADP, Networks Pathways, Techniques, Valine, and glutamicum, myown <span data-person-type="author" class="authorEditorList "><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Tobias Bartek" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/0"><span itemprop="name">T. Bartek</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bastian Blombach" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/1"><span itemprop="name">B. Blombach</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Enrico Zönnchen" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/2"><span itemprop="name">E. Zönnchen</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Pia Makus" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/3"><span itemprop="name">P. Makus</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Siegmund Lang" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/4"><span itemprop="name">S. Lang</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bernhard J. Eikmanns" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/5"><span itemprop="name">B. Eikmanns</span></a></span>, </span> and <span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Marco Oldiges" itemprop="url" href="/person/1ea026818f74ee7c252525689e9c0c32c/author/6"><span itemprop="name">M. Oldiges</span></a></span></span>. </span><span class="additional-entrytype-information"><span itemtype="http://schema.org/PublicationIssue" itemscope="itemscope" itemprop="isPartOf"><em><span itemprop="journal">Biotechnol. Prog.</span>, </em> <em><span itemtype="http://schema.org/PublicationVolume" itemscope="itemscope" itemprop="isPartOf"><span itemprop="volumeNumber">26 </span></span>(<span itemprop="issueNumber">2</span>):
<span itemprop="pagination">361--371</span></em> </span>(<em><span>April 2010<meta content="April 2010" itemprop="datePublished"/></span></em>)</span>Fri Feb 09 13:18:17 CET 2018Biotechnol. Prog.apr2361--371Importance of {NADPH} supply for improved {L}-valine formation in {Corynebacterium} glutamicum262010Biological, Cell Corynebacterium Culture Fermentation, Glucose-6-Phosphate Isomerase, Media, Metabolic Metabolome Models, NADP, Networks Pathways, Techniques, Valine, and glutamicum, myown Cofactor recycling is known to be crucial for amino acid synthesis. Hence, cofactor supply was now analyzed for L-valine to identify new targets for an improvement of production. The central carbon metabolism was analyzed by stoichiometric modeling to estimate the influence of cofactors and to quantify the theoretical yield of L-valine on glucose. Three different optimal routes for L-valine biosynthesis were identified by elementary mode (EM) analysis. The modes differed mainly in the manner of NADPH regeneration, substantiating that the cofactor supply may be crucial for efficient L-valine production. Although the isocitrate dehydrogenase as an NADPH source within the tricarboxylic acid cycle only enables an L-valine yield of Y(Val/Glc) = 0.5 mol L-valine/mol glucose (mol Val/mol Glc), the pentose phosphate pathway seems to be the most promising NADPH source. Based on the theoretical calculation of EMs, the gene encoding phosphoglucoisomerase (PGI) was deleted to achieve this EM with a theoretical yield Y(Val/Glc) = 0.86 mol Val/mol Glc during the production phase. The intracellular NADPH concentration was significantly increased in the PGI-deficient mutant. L-Valine yield increased from 0.49 +/- 0.13 to 0.67 +/- 0.03 mol Val/mol Glc, and, concomitantly, the formation of by-products such as pyruvate was reduced.Metabolic engineering of Corynebacterium glutamicum for 2-ketoisovalerate productionhttps://puma.ub.uni-stuttgart.de/bibtex/2bc1670b16ed84beabd8820d13e46b2d2/bastianbastian2018-02-09T13:18:17+01:00Acids, Bacterial, Corynebacterium Deletion, Engineering, Expression, Gene Genes, Genetic Genetically Glucose, Keto Metabolic Modified Networks Organisms, Pathways, and glutamicum, myown <span data-person-type="author" class="authorEditorList "><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Felix S. Krause" itemprop="url" href="/person/13154880de1726a3496ebe8869a0a7468/author/0"><span itemprop="name">F. Krause</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bastian Blombach" itemprop="url" href="/person/13154880de1726a3496ebe8869a0a7468/author/1"><span itemprop="name">B. Blombach</span></a></span>, </span> and <span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bernhard J. Eikmanns" itemprop="url" href="/person/13154880de1726a3496ebe8869a0a7468/author/2"><span itemprop="name">B. Eikmanns</span></a></span></span>. </span><span class="additional-entrytype-information"><span itemtype="http://schema.org/PublicationIssue" itemscope="itemscope" itemprop="isPartOf"><em><span itemprop="journal">Appl. Environ. Microbiol.</span>, </em> <em><span itemtype="http://schema.org/PublicationVolume" itemscope="itemscope" itemprop="isPartOf"><span itemprop="volumeNumber">76 </span></span>(<span itemprop="issueNumber">24</span>):
<span itemprop="pagination">8053--8061</span></em> </span>(<em><span>December 2010<meta content="December 2010" itemprop="datePublished"/></span></em>)</span>Fri Feb 09 13:18:17 CET 2018Appl. Environ. Microbiol.dec248053--8061Metabolic engineering of {Corynebacterium} glutamicum for 2-ketoisovalerate production762010Acids, Bacterial, Corynebacterium Deletion, Engineering, Expression, Gene Genes, Genetic Genetically Glucose, Keto Metabolic Modified Networks Organisms, Pathways, and glutamicum, myown 2-Ketoisovalerate is used as a therapeutic agent, and a 2-ketoisovalerate-producing organism may serve as a platform for products deriving from this 2-keto acid. We engineered the wild type of Corynebacterium glutamicum for the growth-decoupled production of 2-ketoisovalerate from glucose by deletion of the aceE gene encoding the E1p subunit of the pyruvate dehydrogenase complex, deletion of the transaminase B gene ilvE, and additional overexpression of the ilvBNCD genes, encoding the l-valine biosynthetic enzymes acetohydroxyacid synthase (AHAS), acetohydroxyacid isomeroreductase, and dihydroxyacid dehydratase. 2-Ketoisovalerate production was further improved by deletion of the pyruvate:quinone oxidoreductase gene pqo. In fed-batch fermentations at high cell densities, the newly constructed strains produced up to 188 ± 28 mM (21.8 ± 3.2 g liter(-1)) 2-ketoisovalerate and showed a product yield of about 0.47 ± 0.05 mol per mol (0.3 ± 0.03 g per g) of glucose and a volumetric productivity of about 4.6 ± 0.6 mM (0.53 ± 0.07 g liter(-1)) 2-ketoisovalerate per h in the overall production phase. In studying the influence of the three branched-chain 2-keto acids 2-ketoisovalerate, 2-ketoisocaproate, and 2-keto-3-methylvalerate on the AHAS activity, we observed a competitive inhibition of the AHAS enzyme by 2-ketoisovalerate.The pyruvate dehydrogenase complex of Corynebacterium glutamicum: an attractive target for metabolic engineeringhttps://puma.ub.uni-stuttgart.de/bibtex/2ed56a8ffa25fcb7fe239b276b7e52493/bastianbastian2018-02-09T13:18:17+01:00Acid, Amino Butanols, Complex, Corynebacterium Dehydrogenase Engineering, Isobutanol Metabolic Pyruvate Pyruvic Valine, acid and complex dehydrogenase engineering, glutamicum, myown organic production, <span data-person-type="author" class="authorEditorList "><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bernhard J. Eikmanns" itemprop="url" href="/person/111bc42d6baae0b586acdbed655538eb6/author/0"><span itemprop="name">B. Eikmanns</span></a></span>, </span> and <span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bastian Blombach" itemprop="url" href="/person/111bc42d6baae0b586acdbed655538eb6/author/1"><span itemprop="name">B. Blombach</span></a></span></span>. </span><span class="additional-entrytype-information"><span itemtype="http://schema.org/PublicationIssue" itemscope="itemscope" itemprop="isPartOf"><em><span itemprop="journal">J. Biotechnol.</span>, </em> </span>(<em><span>December 2014<meta content="December 2014" itemprop="datePublished"/></span></em>)</span>Fri Feb 09 13:18:17 CET 2018J. Biotechnol.dec339--345The pyruvate dehydrogenase complex of {Corynebacterium} glutamicum: an attractive target for metabolic engineering192 Pt B2014Acid, Amino Butanols, Complex, Corynebacterium Dehydrogenase Engineering, Isobutanol Metabolic Pyruvate Pyruvic Valine, acid and complex dehydrogenase engineering, glutamicum, myown organic production, The pyruvate dehydrogenase complex (PDHC) catalyzes the oxidative thiamine pyrophosphate-dependent decarboxylation of pyruvate to acetyl-CoA and CO2. Since pyruvate is a key metabolite of the central metabolism and also the precursor for several relevant biotechnological products, metabolic engineering of this multienzyme complex is a promising strategy to improve microbial production processes. This review summarizes the current knowledge and achievements on metabolic engineering approaches to tailor the PDHC of Corynebacterium glutamicum for the bio-based production of l-valine, 2-ketosiovalerate, pyruvate, succinate and isobutanol and to improve l-lysine production.Corynebacterium glutamicum tailored for efficient isobutanol productionhttps://puma.ub.uni-stuttgart.de/bibtex/2a0a5fcfba6017eb6a61292baef557af7/bastianbastian2018-02-09T13:18:17+01:00Anaerobiosis, Bacterial Bacterial, Butanols, Chromosomes, Corynebacterium Escherichia Fungal Glucose, Lactococcus Metabolic Networks Pathways, Plasmids, Proteins Proteins, Recombinant Saccharomyces and cerevisiae, coli, glutamicum, lactis, myown <span data-person-type="author" class="authorEditorList "><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bastian Blombach" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/0"><span itemprop="name">B. Blombach</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Tanja Riester" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/1"><span itemprop="name">T. Riester</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Stefan Wieschalka" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/2"><span itemprop="name">S. Wieschalka</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Christian Ziert" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/3"><span itemprop="name">C. Ziert</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Jung-Won Youn" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/4"><span itemprop="name">J. Youn</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Volker F. Wendisch" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/5"><span itemprop="name">V. Wendisch</span></a></span>, </span> and <span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bernhard J. Eikmanns" itemprop="url" href="/person/10ff226fcd2ff0614810a1890f8f46f8e/author/6"><span itemprop="name">B. Eikmanns</span></a></span></span>. </span><span class="additional-entrytype-information"><span itemtype="http://schema.org/PublicationIssue" itemscope="itemscope" itemprop="isPartOf"><em><span itemprop="journal">Appl. Environ. Microbiol.</span>, </em> <em><span itemtype="http://schema.org/PublicationVolume" itemscope="itemscope" itemprop="isPartOf"><span itemprop="volumeNumber">77 </span></span>(<span itemprop="issueNumber">10</span>):
<span itemprop="pagination">3300--3310</span></em> </span>(<em><span>May 2011<meta content="May 2011" itemprop="datePublished"/></span></em>)</span>Fri Feb 09 13:18:17 CET 2018Appl. Environ. Microbiol.may103300--3310Corynebacterium glutamicum tailored for efficient isobutanol production772011Anaerobiosis, Bacterial Bacterial, Butanols, Chromosomes, Corynebacterium Escherichia Fungal Glucose, Lactococcus Metabolic Networks Pathways, Plasmids, Proteins Proteins, Recombinant Saccharomyces and cerevisiae, coli, glutamicum, lactis, myown We recently engineered Corynebacterium glutamicum for aerobic production of 2-ketoisovalerate by inactivation of the pyruvate dehydrogenase complex, pyruvate:quinone oxidoreductase, transaminase B, and additional overexpression of the ilvBNCD genes, encoding acetohydroxyacid synthase, acetohydroxyacid isomeroreductase, and dihydroxyacid dehydratase. Based on this strain, we engineered C. glutamicum for the production of isobutanol from glucose under oxygen deprivation conditions by inactivation of l-lactate and malate dehydrogenases, implementation of ketoacid decarboxylase from Lactococcus lactis, alcohol dehydrogenase 2 (ADH2) from Saccharomyces cerevisiae, and expression of the pntAB transhydrogenase genes from Escherichia coli. The resulting strain produced isobutanol with a substrate-specific yield (Y(P/S)) of 0.60 ± 0.02 mol per mol of glucose. Interestingly, a chromosomally encoded alcohol dehydrogenase rather than the plasmid-encoded ADH2 from S. cerevisiae was involved in isobutanol formation with C. glutamicum, and overexpression of the corresponding adhA gene increased the Y(P/S) to 0.77 ± 0.01 mol of isobutanol per mol of glucose. Inactivation of the malic enzyme significantly reduced the Y(P/S), indicating that the metabolic cycle consisting of pyruvate and/or phosphoenolpyruvate carboxylase, malate dehydrogenase, and malic enzyme is responsible for the conversion of NADH + H+ to NADPH + H+. In fed-batch fermentations with an aerobic growth phase and an oxygen-depleted production phase, the most promising strain, C. glutamicum ΔaceE Δpqo ΔilvE ΔldhA Δmdh(pJC4ilvBNCD-pntAB)(pBB1kivd-adhA), produced about 175 mM isobutanol, with a volumetric productivity of 4.4 mM h⁻¹, and showed an overall Y(P/S) of about 0.48 mol per mol of glucose in the production phase.Platform engineering of Corynebacterium glutamicum with reduced pyruvate dehydrogenase complex activity for improved production of L-lysine, L-valine, and 2-ketoisovaleratehttps://puma.ub.uni-stuttgart.de/bibtex/2fc097b674eaff7966119cba97aaacd40/bastianbastian2018-02-09T13:18:17+01:00Acids, Biomass, Complex, Corynebacterium Dehydrogenase Deletion, Down-Regulation, Engineering Expression, Gene Genetic, Glucose, Keto Lysine, Metabolic Networks Pathways, Promoter Pyruvate Recombination, Regions, Valine, and glutamicum, myown <span data-person-type="author" class="authorEditorList "><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Jens Buchholz" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/0"><span itemprop="name">J. Buchholz</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Andreas Schwentner" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/1"><span itemprop="name">A. Schwentner</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Britta Brunnenkan" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/2"><span itemprop="name">B. Brunnenkan</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Christina Gabris" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/3"><span itemprop="name">C. Gabris</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Simon Grimm" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/4"><span itemprop="name">S. Grimm</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Robert Gerstmeir" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/5"><span itemprop="name">R. Gerstmeir</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Ralf Takors" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/6"><span itemprop="name">R. Takors</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bernhard J. Eikmanns" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/7"><span itemprop="name">B. Eikmanns</span></a></span>, </span> and <span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bastian Blombach" itemprop="url" href="/person/1671300cf6c01886cf28889b6f3b9a19e/author/8"><span itemprop="name">B. Blombach</span></a></span></span>. </span><span class="additional-entrytype-information"><span itemtype="http://schema.org/PublicationIssue" itemscope="itemscope" itemprop="isPartOf"><em><span itemprop="journal">Appl. Environ. Microbiol.</span>, </em> <em><span itemtype="http://schema.org/PublicationVolume" itemscope="itemscope" itemprop="isPartOf"><span itemprop="volumeNumber">79 </span></span>(<span itemprop="issueNumber">18</span>):
<span itemprop="pagination">5566--5575</span></em> </span>(<em><span>September 2013<meta content="September 2013" itemprop="datePublished"/></span></em>)</span>Fri Feb 09 13:18:17 CET 2018Appl. Environ. Microbiol.sep185566--5575Platform engineering of {Corynebacterium} glutamicum with reduced pyruvate dehydrogenase complex activity for improved production of {L}-lysine, {L}-valine, and 2-ketoisovalerate792013Acids, Biomass, Complex, Corynebacterium Dehydrogenase Deletion, Down-Regulation, Engineering Expression, Gene Genetic, Glucose, Keto Lysine, Metabolic Networks Pathways, Promoter Pyruvate Recombination, Regions, Valine, and glutamicum, myown Exchange of the native Corynebacterium glutamicum promoter of the aceE gene, encoding the E1p subunit of the pyruvate dehydrogenase complex (PDHC), with mutated dapA promoter variants led to a series of C. glutamicum strains with gradually reduced growth rates and PDHC activities. Upon overexpression of the l-valine biosynthetic genes ilvBNCE, all strains produced l-valine. Among these strains, C. glutamicum aceE A16 (pJC4 ilvBNCE) showed the highest biomass and product yields, and thus it was further improved by additional deletion of the pqo and ppc genes, encoding pyruvate:quinone oxidoreductase and phosphoenolpyruvate carboxylase, respectively. In fed-batch fermentations at high cell densities, C. glutamicum aceE A16 Δpqo Δppc (pJC4 ilvBNCE) produced up to 738 mM (i.e., 86.5 g/liter) l-valine with an overall yield (YP/S) of 0.36 mol per mol of glucose and a volumetric productivity (QP) of 13.6 mM per h [1.6 g/(liter × h)]. Additional inactivation of the transaminase B gene (ilvE) and overexpression of ilvBNCD instead of ilvBNCE transformed the l-valine-producing strain into a 2-ketoisovalerate producer, excreting up to 303 mM (35 g/liter) 2-ketoisovalerate with a YP/S of 0.24 mol per mol of glucose and a QP of 6.9 mM per h [0.8 g/(liter × h)]. The replacement of the aceE promoter by the dapA-A16 promoter in the two C. glutamicum l-lysine producers DM1800 and DM1933 improved the production by 100\% and 44\%, respectively. These results demonstrate that C. glutamicum strains with reduced PDHC activity are an excellent platform for the production of pyruvate-derived products.Engineering Corynebacterium glutamicum for the production of pyruvatehttps://puma.ub.uni-stuttgart.de/bibtex/246bcc08cb2281fd8c7391745cce2ec97/bastianbastian2018-02-09T13:18:17+01:00Acid, Corynebacterium Deletion, Engineering Expression, Gene Glucose, Metabolic Networks Pathways, Pyruvic Valine, and glutamicum, myown <span data-person-type="author" class="authorEditorList "><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Stefan Wieschalka" itemprop="url" href="/person/148b87aa35f4559e7a9ead73d1df42fd1/author/0"><span itemprop="name">S. Wieschalka</span></a></span>, </span><span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bastian Blombach" itemprop="url" href="/person/148b87aa35f4559e7a9ead73d1df42fd1/author/1"><span itemprop="name">B. Blombach</span></a></span>, </span> and <span><span itemtype="http://schema.org/Person" itemscope="itemscope" itemprop="author"><a title="Bernhard J. Eikmanns" itemprop="url" href="/person/148b87aa35f4559e7a9ead73d1df42fd1/author/2"><span itemprop="name">B. Eikmanns</span></a></span></span>. </span><span class="additional-entrytype-information"><span itemtype="http://schema.org/PublicationIssue" itemscope="itemscope" itemprop="isPartOf"><em><span itemprop="journal">Appl. Microbiol. Biotechnol.</span>, </em> <em><span itemtype="http://schema.org/PublicationVolume" itemscope="itemscope" itemprop="isPartOf"><span itemprop="volumeNumber">94 </span></span>(<span itemprop="issueNumber">2</span>):
<span itemprop="pagination">449--459</span></em> </span>(<em><span>April 2012<meta content="April 2012" itemprop="datePublished"/></span></em>)</span>Fri Feb 09 13:18:17 CET 2018Appl. Microbiol. Biotechnol.apr2449--459Engineering {Corynebacterium} glutamicum for the production of pyruvate942012Acid, Corynebacterium Deletion, Engineering Expression, Gene Glucose, Metabolic Networks Pathways, Pyruvic Valine, and glutamicum, myown A Corynebacterium glutamicum strain with inactivated pyruvate dehydrogenase complex and a deletion of the gene encoding the pyruvate:quinone oxidoreductase produces about 19 mM L: -valine, 28 mM L: -alanine and about 55 mM pyruvate from 150 mM glucose. Based on this double mutant C. glutamicum △aceE △pqo, we engineered C. glutamicum for efficient production of pyruvate from glucose by additional deletion of the ldhA gene encoding NAD(+)-dependent L: -lactate dehydrogenase (LdhA) and introduction of a attenuated variant of the acetohydroxyacid synthase (△C-T IlvN). The latter modification abolished overflow metabolism towards L: -valine and shifted the product spectrum to pyruvate production. In shake flasks, the resulting strain C. glutamicum △aceE △pqo △ldhA △C-T ilvN produced about 190 mM pyruvate with a Y (P/S) of 1.36 mol per mol of glucose; however, it still secreted significant amounts of L: -alanine. Additional deletion of genes encoding the transaminases AlaT and AvtA reduced L: -alanine formation by about 50\%. In fed-batch fermentations at high cell densities with adjusted oxygen supply during growth and production (0-5\% dissolved oxygen), the newly constructed strain C. glutamicum △aceE △pqo △ldhA △C-T ilvN △alaT △avtA produced more than 500 mM pyruvate with a maximum yield of 0.97 mol per mole of glucose and a productivity of 0.92 mmol g ((CDW)) (-1) h(-1) (i.e., 0.08 g g((CDW)) (-1) h(-1)) in the production phase.