Pharmaceuticals for treating patient with excessive lactate production and related acidemia are disclosed. Pharmaceuticals include glutamate, aspartate, BCAA, pyruvate, malate, oxaloacetate, -ketoglutarate, AST, ALT, PLP, MDH and GPDH, Lodoxamite and Oxamate. The mechanism is that invented pharmaceuticals inhibit LDH and enhance malate/aspartate shuttle activity.

Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to have reduced levels or activity of one or more alcohol dehydrogenases or aldehyde reductases thereby increasing the production of benzylisoquinoline alkaloids and/or benzylisoquinoline alkaloid precursors.

Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to have reduced levels or activity of one or more alcohol dehydrogenases or aldehyde reductases thereby increasing the production of benzylisoquinoline alkaloids and/or benzylisoquinoline alkaloid precursors.

The invention relates to a recombinant cell, preferably a yeast cell comprising: a) one or more heterologous genes encoding a glycerol dehydrogenase activity; b) one or more genes encoding a dihydroxyacetone kinase (E.C. 2.7.1.28 and/or E.C. 2.7.1.29); c) one or more heterologous genes encoding a ribulose-1,5-biphosphate carboxylase oxygenase (EC 4.1.1.39, RuBisCO); and d) one or more heterologous genes encoding a phosphoribulokinase (EC 2.7.1.19, PRK); and optionally e) one or more heterologous genes encoding for a glycerol transporter. This cell can be used for the production of ethanol and advantageously produces little or no glycerol.

The present invention relates to a eukaryotic cell that is genetically modified comprising one or more heterologous gene encoding: a) D-glucose-6-phosphate dehydrogenase and/or b) 6-phosphogluconate dehydrogenase; and/or c) glucose dehydrogenase, gluconolactonase and gluconate kinase,
wherein a), b) and glucose dehydrogenase in c) are NAD.sup.+ dependent.

The present invention is in the field of producing organic acids and other useful chemicals via biological fermentation using glycerol as a source of carbon. Novel microorganisms and fermentation processes are described that are capable of converting glycerol to useful organic acids in high yield and high purity.

The present invention provides recombinant microorganisms comprising an isobutanol producing metabolic pathway and methods of using said recombinant microorganisms to produce isobutanol. In various aspects of the invention, the recombinant microorganisms may comprise a modification resulting in the reduction of pyruvate decarboxylase and/or glycerol-3-phosphate dehydrogenase activity. In various embodiments described herein, the recombinant microorganisms may be microorganisms of the Saccharomyces clade, Crabtree-negative yeast microorganisms, Crabtree-positive yeast microorganisms, post-WGD (whole genome duplication) yeast microorganisms, pre-WGD (whole genome duplication) yeast microorganisms, and non-fermenting yeast microorganisms.

Provided are a genetically engineered yeast cell having increased activity of SUL1, STR3, HXT7, ERR1, GRX8, MXR1, GRE1, MRK1, AAD10 or a combination thereof, compared to a parent cell, and also having acid tolerance, a method of preparing the same, and a method of producing lactate using the same.

Provided herein are glycerol-3-phosphate dehydrogenase (GPD) enzymes with increased K.sub.M for NADH and GPD enzymes with substantially the same affinity for NADH and NADPH and/or are feedback inhibited by glycerol-3-phosphate. Also provided herein are recombinant microorganisms comprising a heterologous gene encoding GPD and a deletion or disruption in an endogenous gene encoding GPD. Also provided are recombinant microorganisms comprising a heterologous gene encoding GPD and a butanol biosynthetic pathway. Further provided are methods of producing butanol comprising providing the recombinant microorganisms described herein and contacting the recombinant microorganism with at least one fermentable carbon substrate under conditions wherein butanol is produced.

The present invention provides recombinant microorganisms comprising an isobutanol producing metabolic pathway and methods of using said recombinant microorganisms to produce isobutanol. In various aspects of the invention, the recombinant microorganisms may comprise a modification resulting in the reduction of pyruvate decarboxylase and/or glycerol-3-phosphate dehydrogenase activity. In various embodiments described herein, the recombinant microorganisms may be microorganisms of the Saccharomyces clade, Crabtree-negative yeast microorganisms, Crabtree-positive yeast microorganisms, post-WGD (whole genome duplication) yeast microorganisms, pre-WGD (whole genome duplication) yeast microorganisms, and non-fermenting yeast microorganisms.