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Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum
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Inhibitory effects are major drawbacks in bio-production and hard to engineer. This work nicely demonstrated how transcriptome analysis helps to identify a key transcriptional regulator, whose overexpression can restore cellular fitness at high product concentrations. This improved production by 38%.
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Chung, S.C., Park, J.S., Yun, J., Park, J.H., Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum. Metab Eng 40 (2017), 157–164 Inhibitory effects are major drawbacks in bio-production and hard to engineer. This work nicely demonstrated how transcriptome analysis helps to identify a key transcriptional regulator, whose overexpression can restore cellular fitness at high product concentrations. This improved production by 38%.
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Bracher, J.M., Verhoeven, M.D., Wisselink, H.W., Crimi, B., Nijland, J.G., Driessen, A.J.M., Klaassen, P., van Maris, A.J.A., Daran, J.G., Pronk, J.T., The Penicillium chrysogenum transporter PcAraT enables high-affinity, glucose-insensitive L-arabinose transport in Saccharomyces cerevisiae. Biotechnol Biofuels, 11, 2018, 63.
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Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge: a multi-omics perspective
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This highly elaborated study demonstrates the extra value of integrating multi-omics data for deciphering microbial metabolism and the regulation thereof. It was shown that the maintenance of cell viability during simultaneous nutrient limitation and salt stress is the result of massive changes in proteome, metabolome and transcriptome, which in sum, however, only entail local changes in metabolic flux. The changes all contribute to maintain homeostasis. An isolated view on only one omics level would have completely distorted the picture of the stress response ofB. subtilis.
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Kohlstedt, M., Sappa, P.K., Meyer, H., Maass, S., Zaprasis, A., Hoffmann, T., Becker, J., Steil, L., Hecker, M., van Dijl, J.M., et al. Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge: a multi-omics perspective. Environ Microbiol 16 (2014), 1898–1917 This highly elaborated study demonstrates the extra value of integrating multi-omics data for deciphering microbial metabolism and the regulation thereof. It was shown that the maintenance of cell viability during simultaneous nutrient limitation and salt stress is the result of massive changes in proteome, metabolome and transcriptome, which in sum, however, only entail local changes in metabolic flux. The changes all contribute to maintain homeostasis. An isolated view on only one omics level would have completely distorted the picture of the stress response ofB. subtilis.
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Efficient 3-hydroxybutyrate production by quiescent Escherichia coli microbial cell factories is facilitated by indole-induced proteomic and metabolomic changes
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This study is an impressive example for the successful application of proteome and metabolome analysis in metabolic engineering. Deciphering the connection between high malonyl-CoA levels and protein-inactivation through malonylation was crucial to optimize the heterologous pinosylvin pathway inE. coli.
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Xu, J.Y., Xu, Y., Chu, X., Tan, M., Ye, B.C., Protein acylation affects the artificial biosynthetic pathway for pinosylvin production in engineered E. coli. ACS Chem Biol, 2018 This study is an impressive example for the successful application of proteome and metabolome analysis in metabolic engineering. Deciphering the connection between high malonyl-CoA levels and protein-inactivation through malonylation was crucial to optimize the heterologous pinosylvin pathway inE. coli.
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ACS Chem Biol
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Xu, J.Y.1
Xu, Y.2
Chu, X.3
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Ye, B.C.5
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Frontiers of high-throughput metabolomics
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Zampieri, M., Sekar, K., Zamboni, N., Sauer, U., Frontiers of high-throughput metabolomics. Curr Opin Chem Biol 36 (2017), 15–23.
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Sevin, D.C., Kuehne, A., Zamboni, N., Sauer, U., Biological insights through nontargeted metabolomics. Curr Opin Biotechnol 34 (2015), 1–8.
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A review of nanoscale LC-ESI for metabolomics and its potential to enhance the metabolome coverage
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Chetwynd, A.J., David, A., A review of nanoscale LC-ESI for metabolomics and its potential to enhance the metabolome coverage. Talanta 182 (2018), 380–390.
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Talanta
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Chetwynd, A.J.1
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42
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85017430967
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Metabolomics-driven approach to solving a CoA imbalance for improved 1-butanol production in Escherichia coli
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The supply of carbon building blocks, redox power and energy is most crucial for production and can often be deduced by stoichiometric considerations. This work is a bracing demonstration that production can also be limited by metabolites, that do not stoichiometrically ‘appear’ in the desired product. In 1BOH producingE. coli, the CoA level is imbalanced thus limiting pathway flux and additionally inducing formation of undesired by-products. Resolving this CoA imbalance improved production by 22%.
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Ohtake, T., Pontrelli, S., Lavina, W.A., Liao, J.C., Putri, S.P., Fukusaki, E., Metabolomics-driven approach to solving a CoA imbalance for improved 1-butanol production in Escherichia coli. Metab Eng 41 (2017), 135–143 The supply of carbon building blocks, redox power and energy is most crucial for production and can often be deduced by stoichiometric considerations. This work is a bracing demonstration that production can also be limited by metabolites, that do not stoichiometrically ‘appear’ in the desired product. In 1BOH producingE. coli, the CoA level is imbalanced thus limiting pathway flux and additionally inducing formation of undesired by-products. Resolving this CoA imbalance improved production by 22%.
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Metab Eng
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, pp. 135-143
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Ohtake, T.1
Pontrelli, S.2
Lavina, W.A.3
Liao, J.C.4
Putri, S.P.5
Fukusaki, E.6
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43
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85047063076
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Metabolome analysis-based design and engineering of a metabolic pathway in Corynebacterium glutamicum to match rates of simultaneous utilization of D-glucose and L-arabinose
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Kawaguchi, H., Yoshihara, K., Hara, K.Y., Hasunuma, T., Ogino, C., Kondo, A., Metabolome analysis-based design and engineering of a metabolic pathway in Corynebacterium glutamicum to match rates of simultaneous utilization of D-glucose and L-arabinose. Microb Cell Fact, 17, 2018, 76.
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Microb Cell Fact
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Kawaguchi, H.1
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Hara, K.Y.3
Hasunuma, T.4
Ogino, C.5
Kondo, A.6
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44
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Analysis of intracellular metabolites from microorganisms: quenching and extraction protocols
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Pinu, F.R., Villas-Boas, S.G., Aggio, R., Analysis of intracellular metabolites from microorganisms: quenching and extraction protocols. Metabolites, 7, 2017.
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Metabolites
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Pinu, F.R.1
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45
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34249088019
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Sampling for metabolome analysis of microorganisms
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Bolten, C.J., Kiefer, P., Letisse, F., Portais, J.C., Wittmann, C., Sampling for metabolome analysis of microorganisms. Anal Chem 79 (2007), 3843–3849.
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(2007)
Anal Chem
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Bolten, C.J.1
Kiefer, P.2
Letisse, F.3
Portais, J.C.4
Wittmann, C.5
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46
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52449131843
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Appropriate sampling for intracellular amino acid analysis in five phylogenetically different yeasts
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Bolten, C.J., Wittmann, C., Appropriate sampling for intracellular amino acid analysis in five phylogenetically different yeasts. Biotechnol Lett 30 (2008), 1993–2000.
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(2008)
Biotechnol Lett
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, pp. 1993-2000
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Bolten, C.J.1
Wittmann, C.2
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47
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33847691476
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Fluxome analysis using GC–MS
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Wittmann, C., Fluxome analysis using GC–MS. Microb Cell Fact, 6, 2007, 6.
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Microb Cell Fact
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, pp. 6
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Wittmann, C.1
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49
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78149407462
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Metabolic fluxes and beyond-systems biology understanding and engineering of microbial metabolism
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Kohlstedt, M., Becker, J., Wittmann, C., Metabolic fluxes and beyond-systems biology understanding and engineering of microbial metabolism. Appl Microbiol Biotechnol 88 (2010), 1065–1075.
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(2010)
Appl Microbiol Biotechnol
, vol.88
, pp. 1065-1075
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Kohlstedt, M.1
Becker, J.2
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50
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13C-based flux analysis
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13C-based flux analysis. Mol Syst Biol, 2, 2006, 62.
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Mol Syst Biol
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Sauer, U.1
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51
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85031825399
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13C metabolic flux analysis and metabolic engineering of the rumen bacterium Basfia succiniciproducens
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13C metabolic flux analysis and metabolic engineering of the rumen bacterium Basfia succiniciproducens. Metab Eng 44 (2017), 198–212.
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(2017)
Metab Eng
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Lange, A.1
Becker, J.2
Schulze, D.3
Cahoreau, E.4
Portais, J.C.5
Haefner, S.6
Schröder, H.7
Krawczyk, J.8
Zelder, O.9
Wittmann, C.10
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52
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84884531356
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Systems-wide analysis and engineering of metabolic pathway fluxes in bio-succinate producing Basfia succiniciproducens
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Becker, J., Reinefeld, J., Stellmacher, R., Schäfer, R., Lange, A., Meyer, H., Lalk, M., Zelder, O., von Abendroth, G., Schröder, H., et al. Systems-wide analysis and engineering of metabolic pathway fluxes in bio-succinate producing Basfia succiniciproducens. Biotechnol Bioeng 110 (2013), 3013–3023.
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Biotechnol Bioeng
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Becker, J.1
Reinefeld, J.2
Stellmacher, R.3
Schäfer, R.4
Lange, A.5
Meyer, H.6
Lalk, M.7
Zelder, O.8
von Abendroth, G.9
Schröder, H.10
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53
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84941217806
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Top value platform chemicals: bio-based production of organic acids
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Becker, J., Lange, A., Fabarius, J., Wittmann, C., Top value platform chemicals: bio-based production of organic acids. Curr Opin Biotechnol 36 (2015), 168–175.
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(2015)
Curr Opin Biotechnol
, vol.36
, pp. 168-175
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Becker, J.1
Lange, A.2
Fabarius, J.3
Wittmann, C.4
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54
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10444258178
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Metabolic fluxes in Corynebacterium glutamicum during lysine production with sucrose as carbon source
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Wittmann, C., Kiefer, P., Zelder, O., Metabolic fluxes in Corynebacterium glutamicum during lysine production with sucrose as carbon source. Appl Environ Microbiol 70 (2004), 7277–7287.
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(2004)
Appl Environ Microbiol
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Wittmann, C.1
Kiefer, P.2
Zelder, O.3
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55
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85047015170
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Lysine production from the sugar alcohol mannitol: design of the cell factory Corynebacterium glutamicum SEA-3 through integrated analysis and engineering of metabolic pathway fluxes
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13C flux analysis was iteratively used to design a strain for lysine production from the third-generation substrate mannitol. This finally led to the design of production independent from the PP pathway. An NADPH-supplying EMP pathway was the key to success for high-level lysine production from mannitol.
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13C flux analysis was iteratively used to design a strain for lysine production from the third-generation substrate mannitol. This finally led to the design of production independent from the PP pathway. An NADPH-supplying EMP pathway was the key to success for high-level lysine production from mannitol.
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(2018)
Metab Eng
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Hoffmann, S.L.1
Jungmann, L.2
Schiefelbein, S.3
Peyriga, L.4
Cahoreau, E.5
Portais, J.C.6
Becker, J.7
Wittmann, C.8
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56
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84884271403
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Core fluxome and metafluxome of lactic acid bacteria under simulated cocoa pulp fermentation conditions
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Adler, P., Bolten, C.J., Dohnt, K., Hansen, C.E., Wittmann, C., Core fluxome and metafluxome of lactic acid bacteria under simulated cocoa pulp fermentation conditions. Appl Environ Microbiol 79 (2013), 5670–5681.
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(2013)
Appl Environ Microbiol
, vol.79
, pp. 5670-5681
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Adler, P.1
Bolten, C.J.2
Dohnt, K.3
Hansen, C.E.4
Wittmann, C.5
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57
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84904910796
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The key to acetate: metabolic fluxes of acetic acid bacteria under cocoa pulp fermentation-simulating conditions
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Adler, P., Frey, L.J., Berger, A., Bolten, C.J., Hansen, C.E., Wittmann, C., The key to acetate: metabolic fluxes of acetic acid bacteria under cocoa pulp fermentation-simulating conditions. Appl Environ Microbiol 80 (2014), 4702–4716.
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(2014)
Appl Environ Microbiol
, vol.80
, pp. 4702-4716
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Adler, P.1
Frey, L.J.2
Berger, A.3
Bolten, C.J.4
Hansen, C.E.5
Wittmann, C.6
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58
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85046410120
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13C metabolic network analysis with combined labeling analysis by GC/MS, LC/MS, 1D, and 2D NMR
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This work impressively shows the analysis of metabolic fluxes in an industrial process for the production of riboflavin by the fungusA. gossypii: a highly complex fermentation set-up with multiple phases (oil, liquid, solid) and complex nutrient compounds. The flux analysis identified the carbon-one supply as time-specific bottleneck and provided a superior bioprocess with 45% increased riboflavin titer.
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13C metabolic network analysis with combined labeling analysis by GC/MS, LC/MS, 1D, and 2D NMR. Metab Eng 47 (2018), 357–373 This work impressively shows the analysis of metabolic fluxes in an industrial process for the production of riboflavin by the fungusA. gossypii: a highly complex fermentation set-up with multiple phases (oil, liquid, solid) and complex nutrient compounds. The flux analysis identified the carbon-one supply as time-specific bottleneck and provided a superior bioprocess with 45% increased riboflavin titer.
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(2018)
Metab Eng
, vol.47
, pp. 357-373
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Schwechheimer, S.K.1
Becker, J.2
Peyriga, L.3
Portais, J.C.4
Sauer, D.5
Müller, R.6
Hoff, B.7
Haefner, S.8
Schröder, H.9
Zelder, O.10
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59
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84954320141
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Biotechnology of riboflavin
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Schwechheimer, S.K., Park, E.Y., Revuelta, J.L., Becker, J., Wittmann, C., Biotechnology of riboflavin. Appl Microbiol Biotechnol, 2016.
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(2016)
Appl Microbiol Biotechnol
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Schwechheimer, S.K.1
Park, E.Y.2
Revuelta, J.L.3
Becker, J.4
Wittmann, C.5
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60
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85032566480
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13C metabolic flux analysis and metabolic engineering for biochemical production
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13C metabolic flux analysis and metabolic engineering for biochemical production. Adv Biochem Eng Biotechnol 162 (2018), 265–299.
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(2018)
Adv Biochem Eng Biotechnol
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Guo, W.1
Sheng, J.2
Feng, X.3
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61
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85041475002
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Hijacking CRISPR-Cas for high-throughput bacterial metabolic engineering: advances and prospects
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Mougiakos, I., Bosma, E.F., Ganguly, J., van der Oost, J., van Kranenburg, R., Hijacking CRISPR-Cas for high-throughput bacterial metabolic engineering: advances and prospects. Curr Opin Biotechnol 50 (2018), 146–157.
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Curr Opin Biotechnol
, vol.50
, pp. 146-157
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Mougiakos, I.1
Bosma, E.F.2
Ganguly, J.3
van der Oost, J.4
van Kranenburg, R.5
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62
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85042184957
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Genetic engineering of host organisms for pharmaceutical synthesis
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Collins, J.H., Young, E.M., Genetic engineering of host organisms for pharmaceutical synthesis. Curr Opin Biotechnol 53 (2018), 191–200.
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Curr Opin Biotechnol
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Collins, J.H.1
Young, E.M.2
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63
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80052022244
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Metabolic engineering of cellular transport for overproduction of the platform chemical 1,5-diaminopentane in Corynebacterium glutamicum
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Kind, S., Kreye, S., Wittmann, C., Metabolic engineering of cellular transport for overproduction of the platform chemical 1,5-diaminopentane in Corynebacterium glutamicum. Metab Eng 13 (2011), 617–627.
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(2011)
Metab Eng
, vol.13
, pp. 617-627
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Kind, S.1
Kreye, S.2
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64
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30744448213
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Accumulation of homolanthionine and activation of a novel pathway for isoleucine biosynthesis in Corynebacterium glutamicum McbR deletion strains
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Krömer, J.O., Heinzle, E., Schröder, H., Wittmann, C., Accumulation of homolanthionine and activation of a novel pathway for isoleucine biosynthesis in Corynebacterium glutamicum McbR deletion strains. J Bacteriol 188 (2006), 609–618.
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(2006)
J Bacteriol
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, pp. 609-618
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Krömer, J.O.1
Heinzle, E.2
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65
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85009677270
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Pathways at work: metabolic flux analysis of the industrial cell factory Corynebacterium glutamicum
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H. Yukawa M. Inui Springer
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Becker, J., Wittmann, C., Pathways at work: metabolic flux analysis of the industrial cell factory Corynebacterium glutamicum. Yukawa, H., Inui, M., (eds.) Corynebacterium glutamicum — Biology and Biotechnology, 2013, Springer, 217–237.
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(2013)
Corynebacterium glutamicum — Biology and Biotechnology
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Becker, J.1
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66
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1242306261
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High-throughput phenomics: experimental methods for mapping fluxomes
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Sauer, U., High-throughput phenomics: experimental methods for mapping fluxomes. Curr Opin Biotechnol 15 (2004), 58–63.
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Curr Opin Biotechnol
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Sauer, U.1
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68
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84990177186
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Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli
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Kim, M., Rai, N., Zorraquino, V., Tagkopoulos, I., Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli. Nat Commun, 7, 2016, 13090.
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Nat Commun
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Kim, M.1
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69
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Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis
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Wang, J.P., Matthews, M.L., Williams, C.M., Shi, R., Yang, C., Tunlaya-Anukit, S., Chen, H.C., Li, Q., Liu, J., Lin, C.Y., et al. Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis. Nat Commun, 9, 2018, 1579.
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Nat Commun
, vol.9
, pp. 1579
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Wang, J.P.1
Matthews, M.L.2
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Tunlaya-Anukit, S.6
Chen, H.C.7
Li, Q.8
Liu, J.9
Lin, C.Y.10
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