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Showing papers in "Metabolic Engineering in 2006"


Journal ArticleDOI
TL;DR: An efficient algorithm is developed to determine accurate flux confidence intervals and it is demonstrated that confidence intervals obtained with this method closely approximate true flux uncertainty.

424 citations


Journal ArticleDOI
TL;DR: A genome-scale reconstructed metabolic network of Saccharomyces cerevisiae is used to score a number of strategies for metabolic engineering of the redox metabolism that will lead to decreased glycerol and increased ethanol yields on glucose under anaerobic conditions.

394 citations


Journal ArticleDOI
TL;DR: A computational framework termed OptReg that determines the optimal reaction activations/inhibitions and eliminations for targeted biochemical production is introduced and the existence of synergism between reaction deletions and modulations is revealed.

317 citations


Journal ArticleDOI
TL;DR: Surprisingly, over-expression of the ispB gene, which was expected to divert carbon flow from the isoprenoid pathway to quinone biosynthesis, resulted in increased beta-carotene production, and it was demonstrated that chromosomal promoter engineering of the endogenous isopranoid pathway yielded high levels of beta- carotene in a non- Carotenogenic E. coli.

249 citations


Journal ArticleDOI
TL;DR: Advances in carotenoid formation and its regulation are reviewed to illustrate how metabolic engineering experiments have shed light on regulatory mechanisms.

190 citations


Journal ArticleDOI
TL;DR: By applying the bootstrap method a better approximation of (possibly) asymmetric confidence intervals for parameters could be obtained and a dynamical model describing a bio-chemical network is used to evaluate the method.

186 citations


Journal ArticleDOI
TL;DR: Secretion engineering, illustrated here by Xbp1-based reprogramming of the post-translational processing machinery, provides a first insight into mastering a major system bottleneck which impacts biopharmaceutical manufacturing of secreted protein therapeutics.

182 citations


Journal ArticleDOI
TL;DR: The enormous capability of both organisms encourages the development of biotechnological methionine production, whereby the use of metabolic pathway analysis provides valuable advice for future strategies in strain and process improvement.

172 citations


Journal ArticleDOI
TL;DR: The functional expression in Escherichia coli of a plant P450 flavonoid 3', 5'-hydroxylase (F3'5'H) as a fusion protein with a P450 reductase is presented, opening the possibility of the future production of several other hydroxylated flavonoids molecules in E. coli.

165 citations


Journal ArticleDOI
TL;DR: During batch fermentation under controlled microaeration conditions, expression of the NADH oxidase under the control of a yeast promoter lead to large decreases in the intracellular NADH concentration and NADH/NAD+ ratio, which caused a large redistribution of metabolic fluxes.

153 citations


Journal ArticleDOI
TL;DR: Strain VH32 is a W3110 derivative with an inactive PTS that acquired the capacity to utilize glucose as a carbon source and showed improved process performance parameters for recombinant protein production over the wild-type strain.

Journal ArticleDOI
TL;DR: The ML01 yeast enjoys 'Generally Regarded As Safe' status from the FDA and is the first genetically enhanced yeast that has been commercialized and will prevent the formation of noxious biogenic amines produced by lactic acid bacteria in wine.

Journal ArticleDOI
TL;DR: By increasing NADH availability, this study demonstrates an important metabolic engineering approach to improve the efficiency of oxidoreduction-coupled bioprocesses.

Journal ArticleDOI
TL;DR: Elevated ammonium has limited effects on the glycosylation genes associated with the ER and cytosol compared to the genes related with the Golgi, indicating that galactosylation and sialylation inhibition is mainly due to decreased gene expression of galacto-sialyltransferase, sialidase, and CMP-Sialic acid transporter.

Journal ArticleDOI
TL;DR: In this paper, an in-depth analysis of the anaerobic metabolic fluxes of various mutant strains of Escherichia coli overexpressing the Lactococcus lactis pyruvate carboxylase (PYC) for the production of succinate is presented.

Journal ArticleDOI
TL;DR: This is the first reported application of genetic engineering to channel precursor flux to improve clavulanic acid production giving a greater than 2-fold increase over wild type, suggesting that arginine became limiting for biosynthesis.

Journal ArticleDOI
TL;DR: It will be shown that although still not all fluxes are identifiable, the quality of flux estimates can be strongly improved in the instationary case, and statements about the size of some immeasurable pool sizes can be made.

Journal ArticleDOI
TL;DR: Attempts to engineer ketocarotenoid biosynthesis in plants have been successful although there are no reports of nutritionally significant levels of astaxanthin in plant storage organs, so potato tubers were engineered in this study.

Journal ArticleDOI
TL;DR: The preference for one side of the biosynthetic pathway branch in early taxane synthesis is revealed, where transcripts coding for TalphaH are abundant after elicitation with MJ but transcripts encoding the two enzymes for the alternative branch (TDAT and T10betaH) are not highly expressed following elicitation.

Journal ArticleDOI
TL;DR: The observed dependence of breast cancer cells on pentose phosphate pathway activity and glutamine consumption for estradiol-stimulated biosynthesis suggests that these pathways may be targets for estrogen-independent breast cancer therapies.

Journal ArticleDOI
TL;DR: A strain containing a strain containing 6 gene deletions is constructed and its properties are evaluated in batch and in chemostat growth experiments to show that the theoretical predictions are closely matched by the properties of the designed strain.

Journal ArticleDOI
TL;DR: Results indicate that the genetic inactivation of Bax and Bak in recombinant CHO cells can be an effective strategy in delaying the onset of apoptosis in batch and fed-batch cultures.

Journal ArticleDOI
TL;DR: A robust second-generation BioScope: a system for continuous perturbation experiments was presented, and it was observed that the dynamic metabolite concentration profiles obtained were nearly the same, with the exception of the C4 metabolites of the TCA cycle, which might be due to differences in culture age.

Journal ArticleDOI
TL;DR: In the present work, Escherichia coli DH5alpha was metabolically engineered for CoQ(10) production by the introduction of decaprenyl diphosphate synthase gene (ddsA) from Agrobacterium tumefaciens, and lower mevalonate semi-pathways of Streptococcus pneumoniae proved to be superior.

Journal ArticleDOI
TL;DR: A pathway design and optimization scheme that accommodates genetically and/or environmentally derived operational constraints is developed that produces novel pathway designs and leads to the construction of optimal succinate production pathway networks.

Journal ArticleDOI
TL;DR: It is demonstrated impressively that the stabilizing effect of the constructed eda-dependent addiction system can be used for production of enhanced amounts of cyanophycin at a larger scale in recombinant strains of R. eutropha.

Journal ArticleDOI
TL;DR: A computational and mathematical framework using Monte Carlo method in which parameter uncertainty can be addressed through large-scale sampling procedure is applied on the compartmentalized central carbon pathways of Saccharomyces cerevisiae metabolism considering the growth environment of batch and chemostat reactor and integrating information from metabolic flux analysis.

Journal ArticleDOI
TL;DR: A computational and statistical framework based on Metabolic Control Analysis is developed that provides the mathematical basis for the quantification of the interactions between intracellular metabolism and extracellular conditions and it is readily applicable to the identification of optimal ME targets for the improvement of industrial processes.

Journal ArticleDOI
TL;DR: A new beta-carotene ketolase gene (crtW) was cloned from an environmental isolate Sphingomonas sp.

Journal ArticleDOI
TL;DR: Together expression of these activities in E. coli strains optimized for the production of L-phenylalanine resulted in the first completely fermentative production of D-Phg, an important side chain building block for semi-synthetic penicillins and cephalosporins.