Abstract: Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.

Abstract: The present invention relates to a genetically modified yeast cell comprising: —at least one recombinant promoter operably linked to at least one gene encoding a polypeptide or protein supporting the biosynthesis of polypeptides or proteins within said cell, said at least one gene being located at the native genomic locus of the genetically unmodified wild-type yeast cell, wherein the naturally occurring promoter of the at least one gene encoding the biosynthesis supporting polypeptide or protein is inactivated by at least one mutation within said naturally occurring promoter and, —a secretion cassette comprising a recombinant nucleic acid molecule encoding a protein or polypeptide of interest and a method for producing a recombinant protein or polypeptide of interest using such a cell.

Abstract: Provided herein are methods for the production of difunctional alkanes in microorganisms. Also provided are enzymes and nucleic acids encoding such enzymes, associated with the difunctional alkane production from carbohydrates feedstocks in microorganisms. The invention also provides recombinant microorganisms and metabolic pathways for the production of difunctional alkanes.

Abstract: Described is a method for generating conjugated dienes through a biological process. More specifically, the application describes a method for producing conjugated dienes (for example butadiene, isoprene or dimethylbutadiene) from light alkenols via enzymatic dehydration, in particular by making use of an alkenol dehydratase.

Abstract: The present invention provides genetically modified strains of microorganisms that display enhanced tolerance to stress and/or inhibitors such as sodium acetate and vanillin. The enhanced tolerance can be achieved by increasing the expression of a protein of the Sm-like superfamily such as a bacterial Hfq protein and a fungal Sm or Lsm protein. Further, the present invention provides methods of producing alcohol from biomass materials by using the genetically modified microorganisms of the present invention.

Abstract: The present invention relates to amino acid sequences that are directed against RANK-L, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The invention also relates to nucleic acids encoding such amino acid sequences and polypeptides; to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.

Abstract: The present invention relates to isolated polypeptides having protease activity and isolated 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.

Abstract: The present invention provides yeast cells that produce high concentrations of ethanol, culture media and bioreactors comprising the yeast cells, and methods for making and using the yeast cells in efficiently producing ethanol.

Abstract: Provided are isolated polypeptides having glucoamylase activity, catalytic domains, and polynucleotides encoding the polypeptides, catalytic 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.

Abstract: The invention relates to a method for metabolic evolution of a variant of a natural small aromatic molecule product of a metabolic pathway, by somatic in vivo assembly and recombination of said metabolic pathway employing a gene mosaic of at least one gene A, which comprises a) in a single step procedure (i) transforming a cell with at least one gene A having a sequence homology of less than 99.

Abstract: The invention relates to genetically modified Pichia ciferrii cells, to the use thereof and to a method of producing sphingoid bases and sphingolipids.

Abstract: Endogenous Sp35 is a negative regulator for neuronal survival, axon regeneration, oligodendrocyte differentiation and myelination (Negative Regulator). Molecules that block endogenous Sp35 function, such anti-Sp35 antibodies can be used as therapeutics for the treatment of neuron and oligodendrocyte dysfunction. The present invention provides antibodies specific for Sp35, and methods of using such antibodies as antagonists of endogenous Sp35 function. The invention further provides specific hybridoma and phage library-derived monoclonal antibodies, nucleic acids encoding these antibodies, and vectors and host cells comprising these antibodies.

Abstract: This document describes biochemical pathways for producing adipic acid, 6-aminohexanoic acid, 6-hydroxhexanoic acid, hexamethylenediamine, caprolactam, or 1,6-hexanediol by forming one or two terminal functional groups, comprised of carboxyl, amine or hydroxyl group, in a C6 aliphatic backbone substrate. These pathways, metabolic engineering and cultivation strategies described herein rely on the enzymes or homologs accepting methyl ester shielded dicarboxylic acid substrates.

Abstract: Compositions and methods for making and using humanized anti-LPA monoclonal antibodies, and fragments and derivatives thereof, are described.

Abstract: The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated 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.

Abstract: The disclosure relates to method of reducing O-glycosylation levels of the insulin or insulin analog precursor molecule produced by Pichia sp. The present disclosure provides genetically engineered knock-out strains of methylotrophic yeast including Pichia and especially Pichia pastoris by disruption of Protein mannosyl transferase (PMT) genes and rendering them capable of producing heterologous proteins with reduced glycosylation. Vectors, which comprise coding sequences for PMT1, PMT2, PMT4, PMT5, and PMT6 genes, for transforming methylotrophic yeasts are contemplated by the present disclosure. PMT inactivated strains of this disclosure have been deposited at MTCC, Chandigarh. The strains are PMT1/GS115 (MTCC 5515), PMT4/GS115 (MTCC 5516), PMT5/GS115 (MTCC 5517) and PMT6/GS115 (MTCC 5518).

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: Disclosed are a human antibody comprising a human complementarity-determining region (CDR), which binds specifically to c-Met, and a framework region (FR), a polynucleotide encoding the human antibody, an expression vector comprising the polynucleotide, a transformant transformed with the expression vector, a method of producing the human antibody B7 by culturing the transformant, a wound healing composition comprising the human antibody as an active ingredient, a cell regeneration composition comprising the antibody as an active ingredient, and a drug conjugate comprising a drug linked to the human antibody. The c-Met-specific human antibody can function as an HGF mimic that can be used as a wound healing composition. The antibody can be widely used to determine the treatment and prognosis of various diseases, including neuronal infarction, progressive nephropathy, liver cirrhosis, lung fibrosis, kidney injury, liver injury, lung injury, and ulcerative wounds, which are treated by activation of HGF or c-Met.

Abstract: This document describes biochemical pathways for producing pimelic acid, 7-aminoheptanoic acid, 7-hydroxyheptanoic 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 carbon chain elongation enzymes or homologs thereof associated with the cyclohexane carboxylate biosynthesis from Syntrophus aciditrophicus or 2-aminoadipate lysine biosynthesis.

Abstract: This document describes biochemical pathways for producing pimelic acid, 7-aminoheptanoic acid, 7-hydroxyheptanoic 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 fatty acid synthesis pathway and oxidative cleavage of long chain acyl-[acp] intermediates by a monooxgenase (e.g., cytochrome P450) such as that encoded by BioI from microorganisms such as Bacillus subtillis.

Abstract: The present invention relates to isolated polypeptides having organophosphorous hydrolase activity and isolated 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.

Abstract: The invention relates to phosphatases and more in specific to (genetically) modified phosphatases, pharmaceutical compositions comprising (genetically) modified phosphatases and the use of (genetically) modified phosphatases for treating or curing for example sepsis, inflammatory bowel disease or other inflammatory diseases, or renal failure. The invention further relates to a method for producing phosphatases.

Abstract: This document describes biochemical pathways for producing pimelic acid, 7-aminoheptanoic acid, 7-hydroxyheptanoic acid, heptamethylenediamine or 1,7-heptanediol by forming one or two terminal functional groups, each 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 C1 elongation enzymes or homolog associated with coenzyme B biosynthesis.

Abstract: Dihydroxy-acid dehydratase (DHAD) variants that display increased DHAD activity are disclosed. Such enzymes can result in increased production of compounds from DHAD requiring biosynthetic pathways. Also disclosed are isolated nucleic acids encoding the DHAD variants, recombinant host cells comprising the isolated nucleic acid molecules, and methods of producing butanol.

Abstract: Isolated receptors, DNAs encoding such receptors, and pharmaceutical compositions made therefrom, are disclosed. The isolated receptors can be used to regulate an immune response. The receptors are also useful in screening for inhibitors thereof.

Abstract: The document provides methods for biosynthesizing isobutene using one or more isolated enzymes such as one or more of an enoyl-CoA dehydratase, a 2-hydroxyacyl-CoA dehydratase, an isovaleryl-CoA/acyl-CoA dehydrogenase and a mevalonate diphosphate decarboxylase, or using recombinant host cells expressing one or more such enzymes.

Abstract: The present invention provides, in part, an antibody display system that simultaneously uses a secretion and a display mode. A bait complexed with a monovalent antibody fragment can be expressed on the surface of the host cell wherein the fragment may be assayed for antigen binding while full antibody is simultaneously secreted from the host cell. Methods of using the system for identifying antibodies that bind specifically to an antigen of interest are also provided. Polypeptides, polynucleotides and host cells useful for making the antibody display system are also provided along with methods of use thereof.

Abstract: This disclosure relates to novel xylose isomerases and their uses, particularly in fermentation processes that employ xylose-containing media.

Abstract: Provided herein are recombinant yeast cells comprising a deletion or disruption in an endogenous gene encoding Amn1 and a heterologous gene encoding Amn1. Also provided are recombinant yeast cells comprising a heterologous gene encoding Amn1 and an engineered butanol biosynthetic pathway. Further provided are methods of producing isobutanol comprising providing the recombinant yeast cells described herein and culturing the recombinant yeast cells under conditions wherein isobutanol is produced.

Abstract: This document describes biochemical pathways for producing adipic acid, caprolactam, 6-aminohexanoic acid, 6-hydroxyhexanoic acid, hexamethylenediamine or 1,6-hexanediol by forming two terminal functional groups, comprised of carboxyl, amine or hydroxyl groups, in a C6 aliphatic backbone substrate. These pathways, metabolic engineering and cultivation strategies described herein rely on CoA-dependent elongation enzymes or analogues enzymes associated with the carbon storage pathways from polyhydroxyalkanoate accumulating bacteria.

Abstract: The present invention relates to isolated polypeptides having cellulase activity. 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.

Abstract: The invention provides functionalized polypeptides, especially therapeutic polypeptides (e.g., scFv), comprising a linker sequence that can be rapidly and specifically functionalized by the addition of one or functional moieties (e.g., PEG) or binding specificities (e.g., an amino acid sequence with a particular binding specificity). Such functionalized polypeptides are advantageous in that they have improved pharmacokinetic properties (e.g., improved in vivo half-life, tissue penetration and tissue residency time) over non-functionalized polypeptides. Methods for the rapid and reproducible generation of functionalized polypeptides are also provided.

Abstract: Endoglucanase characterized by a decreased degree of activity inhibition by a lignin-derived aromatic compound, and prepared by substituting tryptophan at position 273 in the amino acid sequence of wild-type thermophilic bacterium-derived endoglucanase with an amino acid other than aromatic amino acids.

Abstract: The present invention relates to a method for preparing an adipate ester or thioester. The invention further relates to a method for preparing adipic acid from said ester or thioester. Further the invention provides a number of methods for preparing an intermediate for said ester or thioester. Further the invention relates to a method for preparing 6-amino caproic acid (6-ACA), a method for preparing 5-formyl valeric acid (5-FVA), and a method for preparing caprolactam. Further, the invention relates to a host cell for use in a method according to the invention.

Abstract: The present invention relates to a construct for accomplishing fixation of carbon dioxide and/or reduction of carbon dioxide emission in a heterotrophic microorganism (for example, a heterotrophic fermentation strain, such as E. coli), a vector comprising the construct, a heterotrophic microorganism (for example, a heterotrophic fermentation strain, such as E. coli) comprising the construct or being transformed with the vector, and a method for fixing carbon dioxide and/or reducing carbon dioxide emission in a heterotrophic microorganism (for example, a heterotrophic fermentation strain, such as E. coli).

Abstract: The field of this invention relates to methods for combining genetic elements such that the activity of one of the elements provides a means for identifying, enriching, selecting for, or enhancing the activity of a second element. The invention also includes specific elements and combinations of elements.

Abstract: Embodiments herein generally relate to methods, compositions, systems and uses for enabling bio-production of or increasing bio-production of alcohol molecules by microorganisms. Certain embodiments relate to compositions and methods enabling or increasing the bio-production of 4-carbon alcohol molecules by bacteria. In some embodiments, compositions and methods relate to introducing isobutyryl-CoA isomerase to a culture of microorganisms to enable or increase the bio-production of four-carbon alcohols. Variations of biosynthesis pathways for microbial bio-production of butanol and/or isobutanol are provided.

Abstract: From a bacterial strain isolated from an environmental sample, after enrichment in medium containing 1-butanol as the carbon source, a new enzyme with butanol dehydrogenase activity was identified. The enzyme can convert butyraldehyde to 1-butanol, isobutyraldehyde to isobutanol, as well as 2-butanone to 2-butanol and thus is useful for biosynthesis of butanol in recombinant microbial hosts producing these substrates. The encoding gene, named sadB, was isolated from the strain identified as an isolate of Achromobacter xylosoxidans.

Abstract: The invention provides novel polypeptides having at least one biological activity of cardiotrophin and improved biologic drug-like properties, and polynucleotides encoding the polypeptides of the invention. The polypeptides of the invention can be used therapeutically, such as, for example, in methods of tissue regeneration.

Abstract: Antibodies to human IL-23R are provided, as well as uses thereof, e.g. in treatment of inflammatory, autoimmune, and proliferative disorders.

Abstract: The invention relates to a cell which comprises a nucleotide sequence encoding a xylose isomerase, wherein the amino acid sequence of the xylose isomerase has at least 75% sequence identity to the amino acid sequence set out in SEQ ID NO: 2 and wherein the nucleotide sequence is heterologous to the host. A cell of the invention may be used in a process for producing a fermentation product, such as ethanol. Such a process may comprise fermenting a medium containing a source of xylose with a cell of the invention such that the cell ferments xylose to the fermentation product.

Abstract: The present invention relates to the identification of variants of the sugar transporter AGT1 that provide enhanced fermentation of oligosaccharides when recombinantly expressed in yeast. The invention further relates to polynucleotides encoding the variants, recombinant yeast cells expressing the variants, and use of the recombinant yeast cells to ferment oligosaccharides.

Abstract: Disclosed are an amphipathic peptide-lipase conjugate with enhanced lipase activity, a polynucleotide coding for the conjugate, an expression vector carrying the polynucleotide, a transformant anchoring the expression vector therein, a method for preparing the conjugate, a lipolysis method using the conjugate, and a method for producing biodiesel using the lipase.

Abstract: The present invention relates to mono-specific and multi-specific polypeptide therapeutics that specifically target cells expressing prostate-specific membrane antigen (PSMA) and are useful for the treatment of prostate cancer (e.g., castrate-resistant prostate cancer), tumor-related angiogenesis or benign prostatic hyperplasia (BPH). In one embodiment, the multi-specific polypeptide therapeutics bind both PSMA-expressing cells and the T-cell receptor complex on T cells to induce target-dependent T-cell cytotoxicity, activation and proliferation.

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 invention pertains to an isolated VH single domain antibody comprising a C-terminal modification, where the C-terminal modification comprises a deletion of at least one amino acid residue that eliminates the interaction of a pre-existing antibody with the single domain antibody without interfering with the binding of the single domain antibody with its target.

Abstract: Described are methods and compositions for inhibiting the trimerization of ligands belonging to the TNF superfamily, in particular, inhibiting RANKL trimerization. Accordingly, the methods and compositions provided herein can be used to treat disorders associated with increased RANK signaling, in particular those related to bone loss. Compounds that inhibit trimerization of ligands belonging to the TNF superfamily are also described.

Abstract: Testosteronan, a heparosan analog having the structure [-4-D-GlcUA-?1,4-D-GlcNAc-?1-]n, is produced by testosteronan synthase, a single protein that is a dual-action catalyst that utilizes UDP-GlcUA and UDP-GlcNAc to synthesize a polysaccharide having the structure [-4-D-GlcUA-?1,4-D-GlcNAc-?1-]n.

Abstract: Provided herein are recombinant yeast cells having an active 3-Hydroxypropionic Acid (3-HP) pathway and further comprising a heterologous polynucleotide encoding a non-phosphorylating NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPN). Also described are methods of using the recombinant yeast cells to produce 3-HP and acrylic acid.

Abstract: The present invention provides genetically engineered strains of Pichia capable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.