Abstract: Provided herein are compositions and methods for improved production of acetyl-CoA and acetyl-CoA derived compounds in a host cell. In some embodiments, the host cell is genetically modified to comprise a heterologous nucleotide sequence encoding a phosphoketolase (PK), and a functional disruption of an endogenous enzyme that converts acetyl phosphate to acetate. In some embodiments, the host cell further comprises a heterologous nucleotide sequence encoding a phosphotransacetylase (PTA). In some embodiments, the enzyme that converts acetyl phosphate to acetate is a glycerol-1-phosphatase. In some embodiments, the glycerol-1-phosphatase is GPP1/RHR2. In some embodiments, the glycerol-1-phosphatase is GPP2/HOR2. The compositions and methods described herein provide an efficient route for the heterologous production of acetyl-CoA-derived compounds, including but not limited to, isoprenoids, polyketides, and fatty acids.

Abstract: The invention relates to an isolated nucleic acid sequence comprising a promoter, which is a native sequence of Pichia pastoris comprising the nucleic acid sequence of pCS1 of SEQ ID NO:1, or a functionally active variant thereof which is a size variant, a mutant or hybrid of SEQ ID NO:1, or a combination thereof, expression constructs and recombinant host cells comprising the promoter, and a method of producing a protein of interest under the control of the promoter. It further relates to a method to identify a constitutive promoter from eukaryotic cells, and an isolated nucleic acid sequence comprising a promoter which when operatively linked to a nucleotide sequence encoding a protein of interest directs the expression thereof in a host cell at an expression level that is higher than under control of the native pGAP promoter at high and low growth rates.

Abstract: The present invention relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present invention relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present invention can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.

Abstract: Provided are microorganisms that catalyze the synthesis of chemicals and biochemicals from a suitable carbon source. Also provided are methods of generating such organisms and methods of synthesizing chemicals and biochemicals using such organisms.

Abstract: Disclosed are immunogens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the immunogens and methods of producing the immunogens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the immunogen to the subject.

Abstract: Methyl-lysine affinity reagents created by engineering the 3×MBT methyl-lysine binding domain repeat of lethal (3) malignant brain tumor-like protein 1 (L3MBTL1) are disclosed. In particular, the invention relates to affinity reagents and affinity chromatography media comprising the 3×MBT domain repeat and methods of using such affinity reagents in detection, purification, and proteomic profiling of methylated proteins and peptides.

Abstract: The specification describes an improved serum-free animal cell culture medium, which can used for the production of a protein of interest. Ornithine, or a combination of ornithine and putrescine can be added to serum-free media or chemically defined media to improve viable cell density, to reduce cell doubling time, and to increase the production of a protein of interest.

Abstract: Method for producing Yarrowia lipolytica acid-resistant recombinant lipase utilizing a culture medium without any products of animal origin or non-characterized mixtures such as tryptone, peptone or lactoserum, in addition to its uses. Recombinant strain of Yarrow lipolytica producing an excessive amount of lipase Lip2 referred to as YL-LIP2-6C and filed with the Collection Nationale de Cultures de Microorganismes (C.N.C.M.) under number I 3542, on Dec. 15, 2005 and its uses.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: DNA encoding a monomeric variant of red fluorescent protein eqFP611 comprising an amino acid sequence selected from the group consisting of SEQ ID No. 1, SEQ ID No. 3 and SEQ ID No. 5. DNA comprising a nucleotide sequence selected from the group consisting of SEQ ID No. 2, SEQ ID No. 4 and SEQ ID No. 6.

Abstract: Described is a method for the enzymatic production of butadiene which allows to produce butadiene from crotyl alcohol. Also described are enzyme combinations and compositions containing such enzyme combinations which allow the enzymatic conversion of crotyl alcohol into butadiene. Furthermore, the invention relates to microorganisms which have been genetically modified so as to be able to produce butadiene from crotyl alcohol. Moreover, the invention relates to a method for the enzymatic production of crotyl alcohol from crotonyl-Coenzyme A. The obtained crotyl alcohol can be further converted into butadiene as described herein. Also described are enzyme combinations which allow to convert crotonyl-Coenzyme A into crotyl alcohol as well as (micro)organisms which express such enzyme combinations.

Abstract: Specific polypeptides were identified as bacterial xylose isomerases that are able to provide xylose isomerase activity in yeast cells. The xylose isomerase activity can complete a xylose utilization pathway so that yeast can use xylose in fermentation, such as xylose in biomass hydrolysate.

Abstract: Methods for producing modified polypeptides containing amino acid analogues are disclosed. The invention further provides purified dihydrofolate reductase polypeptides, produced by the methods of the invention, in which the methionine residues have been replaced with homoallylglycine, homoproparglycine, norvaline, norleucine, cis-crotylglycine, trans-crotylglycine, 2-aminoheptanoic acid, 2-butynylglycine and allylglycine.

Abstract: Provided is a method of simultaneous co-integration of multiple nucleic acid sequences into a microbial organism comprising culturing a microbial organism to be transformed until a growth phase is reached in which a random integration is facilitated; and transforming the microbial organism by mixing the cultured microbial organism with a sample to be co-integrated into the microbial organism with, wherein the sample comprises more than one nucleic acid sequence, and the products generated from the method.

Abstract: The disclosure provides TNF-like ligand 1a (TL1a)-binding proteins comprising an antigen binding domain of an antibody which binds specifically to TL1a and inhibits interaction of TL1a and Death Receptor 3 (DR3) and which does not inhibit the interaction of TL1a and Decoy Receptor 3 (DcR3). The disclosure also provides uses of the TL1a-binding proteins.

Abstract: An object of the present invention is to provide a method for converting the coenzyme dependency of enzymes of the medium-chain dehydrogenase/reductase (MDR) family. A further object of the present invention is to provide enzyme variants of the MDR family whose coenzyme dependency is converted by the conversion method and a method for enzymatically producing optically active alcohols using the enzymes. The present inventors developed a novel enzyme conversion method for converting the coenzyme dependency of enzymes of the MDR family, rationally designed enzyme variants that are altered by the enzyme conversion method to be able to use NADPH as a coenzyme from a useful enzyme of the MDR family that uses NADH as a coenzyme, and actually provide variants having such an ability.

Abstract: The present invention relates to glucoamylase variants having improved thermostability. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

Abstract: Disclosed herein are methods of producing alcohol esters during a fermentation by providing alcohol-producing microorganisms which further comprise an engineered polynucleotide encoding a polypeptide having lipase activity.

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: Bispecific EGFR/c-Met antibodies and methods of making and using the molecules.

Abstract: The present invention provides a binding molecule which is capable of binding to the rat, cynomolgus monkey and human LINGO polypeptide, a polynucleotide encoding such binding molecule; an expression vector comprising said polynucleotide; an expression system comprising a polynucleotide capable of producing a binding molecule; an isolated host cell which comprises an expression system as defined above; the use of such binding molecule as a pharmaceutical, especially in the treatment to promote axonal regeneration/plasticity; a pharmaceutical composition comprising said binding molecule; and a method of treatment of diseases associated with axonal degeneration and demyelination.

Abstract: The present invention relates to nanobodies specifically directed against VCAM-1 and to their use in medical imaging and in diagnostic, prognostic and treatment methods.

Abstract: The invention relates to specific binding members, particularly antibodies and active fragments thereof, which recognize an aberrant post-translationally modified, particularly an aberrant glycosylated form of the EGFR. The binding members, particularly antibodies and fragments thereof, of the invention do not bind to EGFR on normal cells in the absence of amplification of the wild-type gene and are capable of binding the de2-7 EGFR at an epitope which is distinct from the junctional peptide. Antibodies of this type are exemplified by the novel antibody 806 whose VH and VL sequences are illustrated as SEQ ID NOs: 2 and 4 and chimeric antibodies thereof as exemplified by ch806.

Abstract: This invention relates to isolated nucleic acid fragments encoding polypeptides involved in post-transcriptional gene silencing. The invention also relates to construction of a recombinant DNA construct encoding all or a portion of the polypeptide involved in post-transcriptional gene silencing, in sense or antisense orientation, wherein expression of the recombinant DNA construct results in production of altered levels in a transformed host cell of the polypeptide involved in post-transcriptional gene silencing.

Abstract: The present invention provides genetically modified eukaryotic host cells that produce isoprenoid precursors or isoprenoid compounds. A subject genetically modified host cell comprises increased activity levels of one or more of mevalonate pathway enzymes, increased levels of prenyltransferase activity, and decreased levels of squalene synthase activity. Methods are provided for the production of an isoprenoid compound or an isoprenoid precursor in a subject genetically modified eukaryotic host cell. The methods generally involve culturing a subject genetically modified host cell under conditions that promote production of high levels of an isoprenoid or isoprenoid precursor compound.

Abstract: Disclosed is a method for the dissociation of cells. Cells are processed under conditions of pH, temperature, and shear to thereby yield a mixture of cell wall ghosts and cytoplasm. Preferably, the cells are jet cooked at an alkaline pH to form an intermediate mixture, and the intermediate mixture is subsequently jet cooked. Generally, the cells become dissociated, whereby at least one separate cell wall component is substantially separate from the dissociated cell walls.

Abstract: Provided are isolated polypeptides having cellobiohydrolase activity, catalytic domains and cellulose binding domains, and polynucleotides encoding the polypeptides, catalytic domains or cellulose binding domains. Also provided are nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains or cellulose binding domains.

Abstract: The invention concerns the field of recombinant gene engineering. It concerns novel introns and compositions comprising such introns as well as a method to improve expression of polypeptides from nucleic acids such as cloned genes with heterologous introns, especially genes encoding antibodies and antibody derived fragments, and the production of various polypeptides in eukaryotic host cells using said novel intron sequences as heterologous introns.

Abstract: Described is a method of introducing multiple nucleic acid molecules into the genome of a cell. The method includes providing a plurality of nucleic acid molecules, each of the plurality of nucleic acid molecules containing (a) a nucleic acid sequence operatively linked to a promoter sequence at the 5? end of the nucleic acid molecule, and (b) an overlapping sequence at the 3? end of the nucleic acid molecule.

Abstract: The present invention provides novels genes encoding methyl butenol (MBO) synthase, methy butenol synthases and their use in methyl butenol production.

Abstract: This document describes biochemical pathways for producing pimelic acid, 7-hydroxyheptanoic acid, 7-aminoheptanoic acid, heptamethylenediamine or 1,7-heptanediol by forming two terminal functional groups, comprised of carboxyl, amine or hydroxyl group, in a C7 aliphatic backbone substrate. These pathways, metabolic engineering and cultivation strategies described herein rely on the CoA-dependent elongation enzymes or analog enzymes associated with the carbon storage pathways from polyhydroxyalkanoate accumulating bacteria.

Abstract: A variant polypeptide having alpha-amylase activity, wherein the variant has an amino acid sequence which, when aligned with the alpha-amylase comprising the sequence set out in SEQ ID NO: 2, comprises at least one substitution of an amino acid residue corresponding to any of amino acids 4, 6, 13, 14, 15, 16, 20, 45, 47, 51, 54, 61, 68, 69, 70, 71, 72, 73, 74, 75, 77, 78, 80, 82, 87, 88, 94, 95, 100, 103, 104, 117, 124, 125, 126, 128, 130, 133, 134, 136, 143, 144, 146, 168, 174, 177, 178, 183, 186, 188, 189, 190, 194, 195, 199, 200, 201, 204, 207, 210, 214, 217, 219, 222, 225, 227, 233, 234, 235, 236, 240, 251, 252, 254, 258, 259, 260, 261, 262, 263, 264, 266, 267, 269, 271, 273, 281, 282, 283, 284, 286, 288, 299, 322, 323, 325, 327, 328, 331, 334, 350, 356, 358, 367, 370, 371, 374, 377, 378, 388, 391, 414, 421, 422, 445, 450, 467, 488, 505, 536, 548, 583, 588, 603, 637, 648, 651, 652, 660, 676, 677, said positions being defined with reference to SEQ ID NO: 2 and wherein the variant has one or more altered pr

Abstract: Disclosed herein are polypeptides which exhibit asparaginase activity and little to no glutaminase activity. The polypeptides have sequences which correspond to W. succinogenes asparaginase, but have an amino acid residue other than proline at amino acid position 121. The polypeptides exhibit higher kinetic rates of asparaginase activity to glutaminase activity as compared to W. succinogenes asparaginase and Elspar®, an E. coli asparaginase.

Abstract: Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to express a zeaxanthin cleavage dioxygenase alone or in combination with recombinant genes encoding UDP-glycosyltransferases (UGTs). Such microorganisms, plants, or plant cells can produce compounds from saffron such as crocetin, crocetin dialdehyde, crocin, or picrocrocin.

Abstract: The present invention relates to a glucose-induced inactivation/degradation-resistant transporter gene and use thereof, and more particularly, to a brewing yeast having excellent assimilation of oligosaccharides (maltose, maltotriose, etc.), an alcoholic beverage prepared using the yeast, a method of producing the alcoholic beverage, etc. More specifically, the present invention relates to a glucose-induced inactivation/degradation-resistant transporter including Mal21p, mutant Mal31p, mutant Mal61p, mutant Mtt1p, mutant Agt1p, etc., a gene encoding the transporter, a method of producing an alcoholic beverage using thereof, and so on.

Abstract: This invention provides the use of AChE as nuclease. The use of AChE in regulating the stability of nucleic acid and cell apoptosis, as well as a series of agents based on the use, including the agents for promoting or inhibiting cell apoptosis, the agents for inhibiting tumors, and the agents for protecting nucleic acid from impairing, are provided.

Abstract: The present invention provides and includes monoclonal antibodies (mAbs) preferentially selective for HER2 antigens, hybridoma lines that secrete these HER2 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect HER2 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble or secreted form of HER2. The present invention also includes an antibody or antibody fragment that is capable of reducing the activity of HER2 in at least one form, including a soluble form or a secreted form. The present invention further includes chimeric antibodies, processes for producing monoclonal and chimeric antibodies or monoclonal or chimeric antibodies, and their therapeutic uses, particularly in the detection of cancer most preferentially in human breast, stomach, and colon.

Abstract: There are provided a DNA construct comprising a suppressor tRNA gene of a non-eukaryote containing no internal promoter functioning in a eukaryotic cell, and a eukaryotic or bacteriophage promoter linked at the 5? end of the tRNA gene, a method for synthesizing a suppressor tRNA by using the DNA construct, and a process for producing protein incorporating a non-natural amino acid by using the same.

Abstract: Variants of a parent albumin having altered plasma half-life compared with a parent albumin are described. Fusion polypeptides and conjugates including the variant albumin are also described. Embodiments include, but are not limited to, a polypeptide which is a variant of albumin, including one or more alterations at one or more positions corresponding to 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119 and 120 in SEQ ID NO: 2.

Abstract: Highly productive D-lactic acid fermentation uses a transformant obtained by introducing into a host cell a polynucleotide encoding a polypeptide according to any one of the following (A) to (C) in such a manner that the polypeptide is expressed, which polypeptide has a D-lactate dehydrogenase activity higher than those of conventional polypeptides: (A) a polypeptide having the amino acid sequence shown in SEQ ID NO:1 or 2; (B) a polypeptide having the same amino acid sequence as shown in SEQ ID NO:1 or 2 except that one or several amino acids are substituted, deleted, inserted and/or added, which polypeptide has a D-lactate dehydrogenase activity; and (C) a polypeptide having an amino acid sequence which has a sequence identity of not less than 80% to the amino acid sequence shown in SEQ ID NO:1 or 2, which polypeptide has a D-lactate dehydrogenase activity.

Abstract: The present invention provides recombinant nucleic acid constructs comprising a xylose isomerase polynucleotide, a recombinant fungal host cell comprising a recombinant xylose isomerase polynucleotide, and related methods.

Abstract: The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

Abstract: Embodiments of the present invention relate to methods for the biosynthesis of di- or trifunctional C7 alkanes in the presence of isolated enzymes or in the presence of a recombinant host cell expressing those enzymes. The di- or trifunctional C7 alkanes are useful as intermediates in the production of nylon-7, nylon-7,x, nylon-x,7, and polyesters.

Abstract: The present inventions relate to the selection and production of specific proteins or peptides with desired properties. The inventions relate to the agents and methods of identifying select peptides or proteins with specific binding properties or greater enzymatic performance from vast numbers of variants.

Abstract: A method of producing a protein of interest (POI) by culturing a recombinant eukaryotic cell line comprising an expression construct comprising a regulatable promoter and a nucleic acid molecule encoding a POI under the transcriptional control of said promoter, comprising the steps a) cultivating the cell line with a basal carbon source repressing the promoter, b) cultivating the cell line with a limited amount of a supplemental carbon source de-repressing the promoter to induce production of the POI at a transcription rate of at least 15% as compared to the native pGAP promoter, and c) producing and recovering the POI; and further an isolated regulatable promoter and a respective expression system.

Abstract: Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to express a mutant AROM polypeptide and/or mutant catechol-O-methyltransferase polypeptide alone or in combination with one or more vanillin biosynthetic enzymes or UDP-glycosyltransferases (UGTs). Such microorganisms, plants, or plant cells can produce vanillin or vanillin beta-D-glucoside.

Abstract: Provided is a chimeric isoprenoid synthase polypeptide including a first domain from a first isoprenoid synthase joined to a second domain from a second, heterologous, isoprenoid synthase, whereby the chimeric isoprenoid synthase is capable of catalyzing the production of isoprenoid reaction products that are not produced in the absence of the second domain of the second, heterologous, isoprenoid synthase. Also provided is a chimeric isoprenoid synthase polypeptide including an asymmetrically positioned heterologous domain, whereby the chimeric isoprenoid synthase is capable of catalyzing the production of isoprenoid reaction products that are not produced when the domain is positioned at its naturally-occurring site in the isoprenoid synthase polypeptide.

Abstract: Engineered strains of the oleaginous yeast Yarrowia lipolytica capable of co-producing coenzyme Q10 and at least one ?-3/?-6 polyunsaturated fatty acid are provided. The strains may also be engineered to co-produce at least one C40 carotenoid. Methods of using the antioxidant products obtained (e.g., biomass and/or pigmented oils) in food and feed applications are also provided.

Abstract: The disclosure provides designer cellulosomes for efficient hydrolysis of cellulosic material and more particularly for the generating of ethanol.

Abstract: The present application relates to the field of glyco-engineering, more specifically to eukaryotic cells wherein both an endoglucosaminidase and a glycoprotein are present. These cells can be used to deglycosylate or partly deglycosylate the (exogenous) glycoprotein, in particular without the need for adding an extra enzyme. Methods are also provided for the application of these cells in protein production. According to one specific aspect, the eukaryotic cells and methods are glyco-engineered yeast cells in which additionally at least one exogenous enzyme needed for complex glycosylation is present, e.g. allowing easier separation of differentially glycosylated glycoproteins.