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Showing papers in "Metabolic Engineering in 2003"


Journal ArticleDOI
TL;DR: It was observed that calculations using QP-based methods can show significant variation in growth rate if the flux variability among alternate optima is high, and the variability inherent in metabolic flux distributions is illustrated.

1,187 citations


Journal ArticleDOI
TL;DR: Engineering the uptake of carbon, the regulatory circuits, central metabolism and the common aromatic pathway including shikimic acid import that have all been targeted to effect higher productivities and lower by-product formation are discussed.

217 citations


Journal ArticleDOI
TL;DR: This study investigated the responses of the Bacillus subtilis transcriptome to the presence of glucose and analyzed the role of the pleiotropic transcriptional regulator CcpA in these responses, finding that CCPA directly represses genes involved in the utilization of secondary carbon sources.

208 citations


Journal ArticleDOI
TL;DR: The linlog framework includes general expressions giving the steady-state fluxes and metabolite concentrations as a function of enzyme levels and extracellular concentrations, and a metabolic design equation that allows direct calculation of required enzyme levels for a desired steady state when control and response coefficients are available.

171 citations


Journal ArticleDOI
TL;DR: Analysis of the carotenoid levels by HPLC revealed a 90% decrease in phytoene levels for the double construct expressing crtB in conjunction with crtI, which suggests that the bacterial genes may form an aggregate complex that allows in vivo activity of all three proteins through substrate channeling.

115 citations


Journal ArticleDOI
TL;DR: In this article, a minireview discusses the recent developments in metabolic engineering and the applications of this approach for improving β-lactam production, including pathway extension, heterologous expression of novel genes in well-characterised strains and introduction of new fermentation processes that replace environmentally damaging chemical methods.

110 citations


Journal ArticleDOI
TL;DR: Results of metabolic flux analysis in continuous cultivations show changes in central metabolism due to the cofactor imbalance imposed by the two-step oxidoreductase reaction of xylose to xylulose.

110 citations


Journal ArticleDOI
TL;DR: The results demonstrate that significant flux amplification in complex pathways involving central carbon metabolism is possible through coordinated overexpression of more than one gene in the pathway.

108 citations


Journal ArticleDOI
TL;DR: Findings from MFA provide cues as to which genes/pathways relevant to fatty acid oxidation, urea production, and gluconeogenesis may be upregulated by plasma supplementation, and are consistent with current knowledge of hepatic amino acid metabolism.

70 citations


Journal ArticleDOI
TL;DR: Redirection of electron flow to more efficient proton pumping branches within respiratory chains as a generally applicable metabolic engineering strategy, which tailors microbial metabolism to the specific requirements of high cell density processes by improving product and biomass yields is presented.

63 citations


Journal ArticleDOI
TL;DR: In this paper, a comparison of transcript and metabolite levels of the TCA cycle revealed strong correlations in expression levels but little coordination in the levels of metabolic intermediates, suggesting that a greater understanding of the regulatory circuits and networks controlling metabolism is required before engineering can become routine.

Journal ArticleDOI
TL;DR: Modification of anti-apoptotic genes can affect multiple cellular properties including response to apoptotic stimuli and cell growth, and this knowledge can be valuable in the design of improved apoptosis inhibitors for biotechnology applications.

Journal ArticleDOI
TL;DR: This review is focused especially in the encouraging initial results obtained with the over-expression of cloned anti-apoptosis genes, from both endogenous and viral origin interfering at mitochondrial and initiator caspases levels.


Journal ArticleDOI
TL;DR: The successful combination of this technology with nuclear magnetic resonance (NMR) analysis, metabolite balancing methods and a mathematical description of 13C-isotope labelings resulting in a powerful tool for quantitative pathway analysis during a batch fermentation is described.

Journal ArticleDOI
TL;DR: A novel Sensor Reactor technology is presented which permits 13C labeling experiments for metabolic flux analysis during large-scale, semi-industrial, (fed-) batch fermentation processes deriving a series of flux maps that document fermentation courses in detail.

Journal ArticleDOI
TL;DR: Recombinant DNA technology is utilized to construct recombinant Escherichia coli (E. coli) strains carrying genes expressing GCHI, PTPS and SPR enzymes, which produce BH4, which was detected as dihydrobiopterin and biopterin, oxidation products of BH 4.

Journal ArticleDOI
TL;DR: IL-6 induces a metabolic state where cellular functions are limited by the mitochondrial energy supply, indicating that IL-1beta-mediated effects on electron transport and substrate oxidation reactions are not likely to significantly impact on ATP synthesis.

Journal ArticleDOI
TL;DR: That relatively low levels of RNAi can inhibit protein synthesis driven by the strong polyhedrin (polh) promoter of AcMNPV, suggests that RNAi will find utility as an in vivo metabolic controller in metabolic engineering studies such as this one pertaining to protein expression.

Journal ArticleDOI
TL;DR: Reports on the rate of the malate-aspartate shuttle, as well as the anaplerotic flux of the glial pyruvate carboxylase reaction are in agreement with the estimations calculated from the proposed model, emphasizing the importance of phosphate activated glutaminase and aspartate aminotransferase in the metabolism of neurotransmitter glutamate.

Journal ArticleDOI
TL;DR: A linear programming (LP) algorithm for calculating minimal pathway distances in metabolic networks is studied and the data confirm that propinquity of genes on the genome implies similarity in function, but suggest that no correlation exists between pathway distance and enzyme function.

Journal ArticleDOI
TL;DR: A Windows program for metabolic engineering analysis and experimental design has been developed, which can be used to predict all the extreme point flux distributions that optimize an objective function while satisfying balances and constraints by using a depth-first search strategy.

Journal ArticleDOI
TL;DR: It is shown, for the first time, that oxidative stress, in combination with glucagon, increases metabolic energy expenditure in cultured cells, and that this effect may be mediated by UCP-2.

Journal ArticleDOI
TL;DR: Investigation of the antithrombotic activity of CAT, superoxide dismutase and CHS derivatives in a rat model of arterial injury induced by ferrous chloride found the conjugate was more effective with respect to deceleration and prevention of arterIAL occlusion.

Journal ArticleDOI
TL;DR: The influence of adipate concentration and dissolved oxygen on production of adipoyl-7-aminodeacetoxycephalosporanic acid by a recombinant strain of Penicillium chrysogenum expressing the expandase gene from Streptomyces clavuligerus was studied in glucose-limited continuous cultures.

Journal ArticleDOI
TL;DR: AAA proteins (ATPases associated with various cellular activities) are likely to play several roles in mediating energy-dependent proteolysis by the proteasome, including ATP binding/hydrolysis, substrate binding/unfolding, opening of the axial gates, and translocation of substrate into the proteolytic chamber.