Microbial cell lines suitable for industrial-scale production of organic acids and methods of making and isolating such cell lines, and using the cell lines for production of organic acids.

A transgenic strain for producing 3-hydroxy-3-methylbutyric acid is provided. The transgenic strain comprises a host cell with an anabolic pathway for converting carbon sources into acetyl-CoA and a plurality of exogenous genes. These exogenous genes comprise genes encoding acetyl-CoA acetyltransferase (AtoB) or acetoacetyl-CoA thiolase (NphT7), and genes encoding hydroxymethylglutaryl-CoA synthetase (MvaS), a gene encoding 3-hydroxy-3-methylglutaconyl-CoA dehydratase (LiuC), a gene encoding 3-methylglutaryl-CoA decarboxylase (AibAB), a gene encoding thioester hydrolase (YciA, TesB, MenI or YqiA). A method for producing 3-hydroxy-3-methylbutyric acid using the above genetically modified strain is also provided.

A transgenic strain for producing 3-hydroxy-3-methylbutyric acid is provided. The transgenic strain comprises a host cell with an anabolic pathway for converting carbon sources into acetyl-CoA and a plurality of exogenous genes. These exogenous genes comprise genes encoding acetyl-CoA acetyltransferase (AtoB) or acetoacetyl-CoA thiolase (NphT7), and genes encoding hydroxymethylglutaryl-CoA synthetase (MvaS), a gene encoding 3-hydroxy-3-methylglutaconyl-CoA dehydratase (LiuC), a gene encoding 3-methylglutaryl-CoA decarboxylase (AibAB), a gene encoding thioester hydrolase (YciA, TesB, MenI or YqiA). A method for producing 3-hydroxy-3-methylbutyric acid using the above genetically modified strain is also provided.

A method for manufacturing a mixed solution comprising propionate and acetate includes adding acid to a fermentation product to obtain an acidified fermentation product comprising propionate and acetate with a pH in the range of 2.5 to 8. The method optionally includes removing carbonate-related compounds from the mixed solution.

A method for manufacturing a mixed solution comprising propionate and acetate includes adding acid to a fermentation product to obtain an acidified fermentation product comprising propionate and acetate with a pH in the range of 2.5 to 8. The method optionally includes removing carbonate-related compounds from the mixed solution.

The invention relates to a method of cell culture where the cells are modified to reduce the level of synthesis of growth and/or productivity inhibitors by the cell. The invention also relates to a method of cell culture for improving cell growth and productivity, in particular in fed-batch culture of mammalian cells at high cell density. The invention further relates to a method of producing cells with improved cell growth and/or productivity in cell culture and to cells obtained or obtainable by such methods.

The invention relates to a method of cell culture where the cells are modified to reduce the level of synthesis of growth and/or productivity inhibitors by the cell. The invention also relates to a method of cell culture for improving cell growth and productivity, in particular in fed-batch culture of mammalian cells at high cell density. The invention further relates to a method of producing cells with improved cell growth and/or productivity in cell culture and to cells obtained or obtainable by such methods.

Cells and cell cultures are provided that have improved tolerance to 3-hydroxypropionic acid (3HP). Genetic modifications to provide a mutated or overexpressed SFA1 gene or other enhancement of 3HP detoxification via a glutathione-dependent dehydrogenase reaction, including medium supplementation with glutathione, may be combined with a 3HP producing metabolic pathway.

Cells and cell cultures are provided that have improved tolerance to 3-hydroxypropionic acid (3HP). Genetic modifications to provide a mutated or overexpressed SFA1 gene or other enhancement of 3HP detoxification via a glutathione-dependent dehydrogenase reaction, including medium supplementation with glutathione, may be combined with a 3HP producing metabolic pathway.

The present invention relates to isolated polypeptides having beta-xylosidase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.