Abstract: The present invention provides for novel metabolic pathways to detoxify biomass-derived acetate via metabolic conversion to ethanol, acetone, or isopropanol. More specifically, the invention provides for a recombinant microorganism comprising one or more native and/or heterologous enzymes that function in one or more first engineered metabolic pathways to achieve: (1) conversion of acetate to ethanol; (2) conversion of acetate to acetone; or (3) conversion of acetate to isopropanol; and one or more native and/or heterologous enzymes that function in one or more second engineered metabolic pathways to produce an electron donor used in the conversion of acetate to less inhibitory compounds; wherein the one or more native and/or heterologous enzymes is activated, unregulated, or downregulated.

Abstract: Disclosed are genetically engineered organisms, such as yeast and bacteria, that have the ability to metabolize atypical phosphorus or sulfur sources. Fermentation methods using the genetically engineered organisms are also described. The fermentation methods are robust processes for the industrial bioproduction of a variety of compounds, including commodities, fine chemicals, and pharmaceuticals.

Abstract: Disclosed are genetically engineered organisms, such as yeast and bacteria, that have the ability to metabolize atypical nitrogen sources, such as melamine and cyanamide. Fermentation methods using the genetically engineered organisms are also described. The methods of the invention are robust processes for the industrial bioproduction of a variety of compounds, including commodities, fine chemicals, and pharmaceuticals.

Abstract: Thermophilic gram-positive anaerobic host cells, for example Thermoanaerobacterium saccharolyticum (“T sacch”), express heterologous biomass degrading enzymes, such as cellulases, and are able to produce useful fermentation products from cellulose. Useful fermentation products include, for example, ethanol, acetic acid, lactic acid or CO2. In order to provide maximum expression and activity levels, biomass degrading enzymes can be expressed from codon-optimized nucleotide sequences, can be expressed under the control of a high-efficiency promoter, and/or can be fused to a signal peptide. In addition, the host cell, for example, a T sacch host cell, can be genetically altered to further improve ethanol production, for example by disrupting the production of organic products other than ethanol.

Abstract: The present invention provides for novel metabolic pathways to reduce or eliminate glycerol production and increase product formation. More specifically, the invention provides for a recombinant microorganism comprising a deletion of one or more native enzymes that function to produce glycerol and/or regulate glycerol synthesis and one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert a carbohydrate source, such as lignocellulose, to a product, such as ethanol, wherein the one or more native and/or heterologous enzymes is activated, upregulated, or downregulated.

Abstract: The present invention provides for novel metabolic pathways to reduce or eliminate glycerol production and increase product formation. More specifically, the invention provides for a recombinant microorganism comprising a deletion of one or more native enzymes that function to produce glycerol and/or regulate glycerol synthesis and one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert a carbohydrate source, such as lignocellulose, to a product, such as ethanol, wherein the one or more native and/or heterologous enzymes is activated, upregulated, or downregulated.

Abstract: The present invention provides for the manipulation of carbon flux in a recombinant host cell to increase the formation of desirable products. The invention relates to cellulose-digesting organisms that have been genetically modified to allow the production of ethanol at a high yield by redirecting carbon flux at key steps of central metabolism.

Abstract: The present invention provides for the manipulation of cofactor usage in a recombinant host cell to increase the formation of desirable products. In some embodiments, the invention provides for a recombinant microorganism comprising a mutation in one or more native enzymes such that their cofactor specificity is altered in such a way that overall cofactor usage in the cell is balanced for a specified pathway and there is an increase in a specific product formation within the cell. In some embodiments, endogenous enzymes are replaced by enzymes with an alternate cofactor specificity from a different species.

Abstract: The present invention provides for novel metabolic pathways to detoxify biomass-derived acetate via metabolic conversion to ethanol, acetone, or isopropanol. More specifically, the invention provides for a recombinant microorganism comprising one or more native and/or heterologous enzymes that function in one or more first engineered metabolic pathways to achieve: (1) conversion of acetate to ethanol; (2) conversion of acetate to acetone; or (3) conversion of acetate to isopropanol; and one or more native and/or heterologous enzymes that function in one or more second engineered metabolic pathways to produce an electron donor used in the conversion of acetate to less inhibitory compounds; wherein the one or more native and/or heterologous enzymes is activated, upregulated, or downregulated.

Abstract: The present invention provides for novel metabolic pathways to reduce or eliminate glycerol production and increase product formation. More specifically, the invention provides for a recombinant microorganism comprising a deletion of one or more native enzymes that function to produce glycerol and/or regulate glycerol synthesis and one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to convert a carbohydrate source, such as lignocellulose, to a product, such as ethanol, wherein the one or more native and/or heterologous enzymes is activated, upregulated, or downregulated.

Abstract: The present invention provides for novel metabolic pathways to convert biomass and other carbohydrate sources to malonyl-CoA derived products, such as hydrocarbons and other bioproducts, under anaerobic conditions and with the net production of ATP. More specifically, the invention provides for a recombinant microorganism comprising one or more native and/or heterologous enzymes that function in one or more engineered metabolic pathways to achieve conversion of a carbohydrate source to, e.g., long-chain hydrocarbons and hydrocarbon derivatives, wherein the one or more native and/or heterologous enzymes is activated, upregulated, downregulated, or deleted. The invention also provides for processes to convert biomass to malonyl-CoA derived products which comprise contacting a carbohydrate source with a recombinant microorganism of the invention.

Abstract: One aspect of the invention relates to a genetically modified thermophilic or mesophilic microorganism, wherein a first native gene is partially, substantially, or completely deleted, silenced, inactivated, or down-regulated, which first native gene encodes a first native enzyme involved in the metabolic production of an organic acid or a salt thereof, thereby increasing the native ability of said thermophilic or mesophilic microorganism to produce lactate or acetate as a fermentation product. In certain embodiments, the aforementioned microorganism further comprises a first non-native gene, which first non-native gene encodes a first non-native enzyme involved in the metabolic production of lactate or acetate. Another aspect of the invention relates to a process for converting lignocellulosic biomass to lactate or acetate, comprising contacting lignocellulosic biomass with a genetically modified thermophilic or mesophilic microorganism.

Abstract: The invention is directed to the heterologous expression of urease in anaerobic thermophilic hosts, such as Thermoanaerobacterium, Thermoanaerobacter, and other related genera. For example, the anaerobic thermophilic host can be T. saccharolyticum. The host cells express the catalytic subunits of the urease enzyme together with the accessory proteins ureDEFG that facilitate protein folding and nickel activation. The invention further relates to the use of urea as a nitrogen source in the growth of microorganisms involved in consolidated bioprocessing systems.

Abstract: The present invention relates to the field of molecular biology and genetic tool development in thermophilic bacteria. In particular, it relates to the use of positive and/or negative selection markers that can be used to efficiently select modified strains of interest. By providing such capabilities, the disclosed invention facilitates the recycling of genetic markers in thermophilic bacterial host cells. The present invention also allows the creation of unmarked strains. The genetic tools disclosed in the present invention are prerequisites for making targeted higher order mutations in a single thermophilic strain background.

Abstract: The present invention provides for novel metabolic pathways leading to propanol, alcohol or polyol formation in a consolidated bioprocessing system (CBP), where lignocellulosic biomass is efficiently converted to such products. More specifically, the invention provides for a recombinant microorganism, where the microorganism expresses one or more native and/or heterologous enzymes; where the one or more enzymes function in one or more engineered metabolic pathways to achieve: (1) conversion of a carbohydrate source to 1,2-propanediol, isopropropanol, ethanol and/or glycerol; (2) conversion of a carbohydrate source to n-propanol and isopropanol; (3) conversion of a carbohydrate source to isopropanol and methanol; or (4) conversion of a carbohydrate source to propanediol and acetone; wherein the one or more native and/or heterologous enzymes is activated, up-regulated or down-regulated.

Abstract: The present invention provides for novel metabolic pathways leading to acrylate formation in a consolidated bio-processing system (CBP) where lignocellulosic biomass is efficiently converted to acrylate. In one such metabolic pathway, pyruvate is converted to lactate, which is converted to lactoyol-CoA, which is converted to acryloyl-CoA, and which is finally converted to acrylate. In another such metabolic pathway, pyruvate is converted to L-?-alanine, which is converted to L-aspartate, which is converted to ?-alanine, which is converted to ?-alanyl-CoA, which is converted to acryloyl-CoA, and which is finally converted to acrylate. In yet another metabolic pathway, pyruvate is converted to lactate, and then lactate is converted directly to acrylate.

Abstract: One aspect of the invention relates to a genetically modified thermophilic or mesophilic microorganism, wherein a first native gene is partially, substantially, or completely deleted, silenced, inactivated, or down-regulated, which first native gene encodes a first native enzyme involved in the metabolic production of an organic acid or a salt thereof, thereby increasing the native ability of said thermophilic or mesophilic microorganism to produce lactate or acetate as a fermentation product. In certain embodiments, the aforementioned microorganism further comprises a first non-native gene, which first non-native gene encodes a first non-native enzyme involved in the metabolic production of lactate or acetate. Another aspect of the invention relates to a process for converting lignocellulosic biomass to lactate or acetate, comprising contacting lignocellulosic biomass with a genetically modified thermophilic or mesophilic microorganism.