Metabolic engineering of Saccharomyces cerevisiae for production of Eicosapentaenoic Acid, using a novel {Delta}5-Desaturase from Paramecium tetraurelia.

Very-long-chain polyunsaturated fatty acids, such as arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have well-documented importance in human health and nutrition. Sustainable production in robust host organisms that do not synthesize them naturally requires the coordinated expression of several heterologous desaturases and elongases. In the present study we show production of EPA in Saccharomyces cerevisiae using glucose as the sole carbon source through expression of five heterologous fatty acid desaturases and an elongase.

Studies of the production of fungal polyketides in Aspergillus nidulans by using systems biology tools.

Many filamentous fungi produce polyketide molecules with great significance as human pharmaceuticals; these molecules include the cholesterol-lowering compound lovastatin, which was originally isolated from Aspergillus terreus. The chemical diversity and potential uses of these compounds are virtually unlimited, and it is thus of great interest to develop a well-described microbial production platform for polyketides. Using genetic engineering tools available for the model organism Aspergillus nidulans, we constructed two recombinant strains, one expressing the Penicillium griseofulvum 6-methylsalicylic acid (6-MSA) synthase gene and one expressing the 6-MSA synthase gene and overexpressing the native xylulose-5-phosphate phosphoketolase gene (xpkA) for increasing the pool of polyketide precursor levels.

Systems analysis unfolds the relationship between the phosphoketolase pathway and growth in Aspergillus nidulans.

Background: Aspergillus nidulans is an important model organism for studies on fundamental eukaryotic cell biology and on industrial processes due to its close relation to A. niger and A. oryzae.

Overexpression of a novel endogenous NADH kinase in Aspergillus nidulans enhances growth.

The complete genome sequence of the filamentous fungi Aspergillus nidulans has paved the way for fundamental research on this industrially important species. To the best of our knowledge, this is the first time a gene encoding for ATP-dependent NADH kinase (ATP:NADH 2'-phosphotransferase, EC 2.7.

Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae.

Background: Growth rate is central to the development of cells in all organisms. However, little is known about the impact of changing growth rates. We used continuous cultures to control growth rate and studied the transcriptional program of the model eukaryote Saccharomyces cerevisiae, with generation times varying between 2 and 35 hours.

Global transcriptional and physiological responses of Saccharomyces cerevisiae to ammonium, L-alanine, or L-glutamine limitation.

The yeast Saccharomyces cerevisiae encounters a range of nitrogen sources at various concentrations in its environment. The impact of these two parameters on transcription and metabolism was studied by growing S. cerevisiae in chemostat cultures with l-glutamine, l-alanine, or l-ammonium in limitation and by growing cells in an excess of ammonium.

Engineering of the redox imbalance of Fusarium oxysporum enables anaerobic growth on xylose.

Dissimilatory nitrate reduction metabolism, of the natural xylose-fermenting fungus Fusarium oxysporum, was used as a strategy to achieve anaerobic growth and ethanol production from xylose. Beneficial alterations of the redox fluxes and thereby of the xylose metabolism were obtained by taking advantage of the regeneration of the cofactor NAD(+) during the denitrification process. In batch cultivations, nitrate sustained growth under anaerobic conditions (1.

Robust multi-scale clustering of large DNA microarray datasets with the consensus algorithm.

Motivation: Hierarchical and relocation clustering (e.g. K-means and self-organizing maps) have been successful tools in the display and analysis of whole genome DNA microarray expression data.

Comparative metabolic network analysis of two xylose fermenting recombinant Saccharomyces cerevisiae strains.

The recombinant xylose fermenting strain Saccharomyces cerevisiae TMB3001 can grow on xylose, but the xylose utilisation rate is low. One important reason for the inefficient fermentation of xylose to ethanol is believed to be the imbalance of redox co-factors. In the present study, a metabolic flux model was constructed for two recombinant S.

Impact of transamination reactions and protein turnover on labeling dynamics in (13)C-labeling experiments.

A dynamic model describing carbon atom transitions in the central metabolism of Saccharomyces cerevisiae is used to investigate the influence of transamination reactions and protein turnover on the transient behavior of (13)C-labeling chemostat experiments. The simulations performed suggest that carbon exchange due to transamination and protein turnover can significantly increase the required time needed for metabolites in the TCA cycle to reach isotopic steady state, which is in agreement with published experimental observations. On the other hand, transamination and protein turnover will speed-up the net rate of incorporation of labeled carbon into some free and protein-bound amino acids.