Abstract: The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.

Abstract: The present invention provides a polynucleotide or a pair of polynucleotides encoding an enzyme having nitrile hydratase (NHase) [E.C. 4.2.1.84] activity. Furthermore, a vector and a host comprising the disclosed polynucleotide or pair of polynucleotides and methods for the production of the same are provided. Moreover, the invention relates to a pair of polypeptides or a fusion protein having NHase activity, an antibody specifically binding to the pair of polypeptides or fusion protein, a primer or probe, which specifically hybridizes under stringent conditions to the disclosed polynucleotide or either one of the pair of polynucleotides, a composition comprising the polynucleotide or pair of polynucleotides, the pair of polypeptides or fusion protein, the antibody and/or one or more primers or probes of the invention and a method for the production of amides comprising the enantioselective conversion of nitriles.

Abstract: Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: The present disclosure relates to a deacetylation hydrolase of a hyaluronic acid a hyaluronic acid deacetylated by same and a derivative thereof. The deacetylated hyaluronic acid and the derivative thereof have the following characteristic: a delayed initial decomposition rate on a living body; minimized decrease of molecular weight and viscosity; accelerated gelation due to a lower gelation temperature than the gelation temperature for a non-deacetylated hyaluronic acid; and an hMSC survival rate that is hardly affected by increased concentration of the deacetylated hyaluronic acid and the derivative thereof in a culture medium. As a result, the deacetylated hyaluronic acid and the derivative thereof can be useful as a bioingredient such a delivery system for a cell, gene, drug, and the like, or a support for tissue engineering, etc.

Abstract: The invention is directed to a cell comprising a nucleic acid encoding an Activation Induced Deaminase (AID) polypeptide, a fusion protein comprising an AID polypeptide, and methods of using a nucleic acid encoding an AID polypeptide.

Abstract: The present invention relates to an arginine deiminase mutant with partial lysine-deficient and preparation and application thereof. The arginine deiminase mutant of the present invention has enzymatic activity of degrading arginine into citruline; compared with the arginine deiminase with the amino acid sequence of SEQ ID NO: 1, the amino acid sequence comprises one or more of K9N, T, K59Q, K66R, A, K93E, A, Q, K111R, A, K119Q, L, M, K121Q, I, K122E, L, K126E, S, R, K178I, E, D, K196I, R, K209G, T, D, K243E, V, R, K249D, Q, K263N, Q, K279Y, T, K293R, H, E, K325V, I, K380T, R, E, and K406E, D, S substitutions. Compared with PEG modified natural derived arginine deiminase, the PEG modified arginine deiminase mutant of the present invention retain better bioactivity; and because the quantity of lysine in arginine deiminase is reduced, the PEG modified products are more uniform and can be applied to clinical treatment of hepatoma, melanoma and the like.

Abstract: The invention provides novel processes for making ethyl-4-cyano-3-hydroxybutyrate, e.g., (R)-ethyl 4-cyano-3-hydroxybutyric acid, and 4-cyano-3-hydroxybutyric acid. The invention provides protocols for making and 4-cyano-3-hydroxybutyric acid and ethyl-4-cyano-3-hydroxybutyrate by whole cell processes, cell lysate processes, “one pot processes” and “multi-pot” processes using a variety of parameters.

Abstract: Provided herein are methods for inducing and stabilizing an enzyme activity. Optionally, the enzyme is in a microorganism capable of producing the enzyme. In some embodiments, the enzyme can be nitrile hydratase, amidase, or asparaginase I. Provided are compositions comprising enzymes or microorganisms having induced and/or stabilized activity. Also provided are methods of delaying a plant development process by exposing a plant or plant part to the enzymes or microorganisms having induced and/or stabilized activity.

Abstract: The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.

Abstract: This invention relates to a novel, bacterial GTP Cyclohydrolase Type IB enzyme, and the crystal structure thereof.

Abstract: The present invention relates to an asparaginase having the width of the pH activity profile which is at least 3.5. Furthermore the invention relates to newly identified asparaginase polypeptide according to any one of SEQ ID NO: 2 or SEQ ID NO: 4 and to variants thereof and to polynucleotide sequences that encode such novel asparaginase variants. Furthermore the invention relates to the use of these novel asparaginase variants in industrial processes.

Abstract: The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.

Abstract: The present invention relates to compounds that are substrates for an enzyme, and upon reaction with the enzyme provide a detectable response, such as an optically detectable response. In particular, the compounds have utility in detecting the presence of a ?-lactamase in a sample. In addition to the compounds, methods are disclosed for analyzing a sample for the presence of a ?-lactmase, for example, as an indicator of expression of a nucleic acid sequence including a sequence coding for a ?-lactmase. Kits are disclosed that include the disclosed compounds and additional components, for example, cells, antibodies, a ?-lactmase or instructions for using the components in an assay.

Abstract: The invention features methods and compositions for diagnosis, including prognosis, of conditions associated with decreased arginine bioavailability (which can result from dysregulated arginine metabolism, e.g., due to increased arginase activity) by assessing in a sample from a subject the ratio of arginine to one or more, usually two or more, modulators of arginine bioavailability. In one embodiment, the ratio of arginine to (ornithine+citrulline) is assessed to aid in diagnosis.

Abstract: The invention provides polypeptides, including enzymes, structural proteins and binding proteins, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. Polypeptides, including enzymes and antibodies, and nucleic acids of the invention can be used in industrial, experimental, food and feed processing, nutritional and pharmaceutical applications, e.g., for food and feed supplements, colorants, neutraceuticals, cosmetic and pharmaceutical needs.

Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: It has surprisingly been discovered that it is possible to use enzymes in deep eutectic solvents (DES). DES's are mixtures of a nitrogen salt or a metal salt and a strong hydrogen bond donor that can be mixed in proportions that form a eutectic point.

Abstract: Methods and composition for generation of arginase variants with high serum persistence are provided. For example, in certain aspects methods for purifying pegylated arginase are described. Furthermore, the invention provides stabilized arginase multimers or pharmaceutical composition thereof.

Abstract: Methods for identifying selective activators of SIRT5 and/or SIRT1 and methods for using these selective activators in the modulation of SIRT5 and/or SIRT1 are provided.

Abstract: The invention provides deimmunized mutant proteins having reduced immunogenicity while exhibiting substantially the same or greater biological activity as the proteins of interst from which they are derived, as exemplified by mutant L-asparaginase that comprises amino acid substitutions compared to wild type L-asparaginase. The invention further provides methods for screening mutant deimmunized proteins that have substantially the same or greater biological activity as a protein of interest, and methods for reducing immunogenicity, without substantially reducing biological activity, of a protein of interest. The invention's compositions and methods are useful in, for example, therapeutic applications by minimizing adverse immune responses by the host mammalian subjects to the protein of interest.

Abstract: The present disclosure relates to polypeptides having nitrilase activity, polynucleotides encoding the polypeptides, and methods of using the polypeptides.

Abstract: The present invention relates to a method for identifying compounds that modulate the activity of sirtuin deacetylase protein family members. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified nicotinamide inhibition and base exchange site of Sir2 and testing the compound for its ability to modulate the activity of the Sir2 protein. Compositions and methods for preventing or treating diseases or disorders associated with Sir2 are also provided.

Abstract: The present invention relates to a protein which exhibits asparaginase activity and which has an amino acid sequence according to SEQ ID NO. 2-SEQ ID NO.10. The advantage of the protein of the present invention is that it exhibits asparaginase activity (EC 3.5.1.1) with a specific activity at acidic, neutral and alkaline pH which is many times higher than the specific activity of wild-type asparaginase.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: The invention relates to a multiple bioreactor system comprising a plurality of bioreactors, a source of pressurised fluid, and distribution means for distributing the fluid to the bioreactors, wherein the bioreactor system includes backpressure creating means presented by, before or after each bioreactor and the source of pressurised fluid such that each backpressure creating means provides a resistance to the flow of the pressurised fluid which is greater than the resistance to flow between each backpressure creating means.

Abstract: A method is provided for improving the solubility of proteins, for example, bacterial toxins. In one embodiment, solubility is improved by introducing point mutations that replace cysteine residues capable of forming intermolecular disulfide bonds with other amino acid residues that do not form such bonds. By abrogating the ability of the cysteine residues to form inter-molecular disulfide bonds, aggregation of the protein is reduced, thereby improving the solubility of the protein. In another embodiment, solubility of the protein is improved by producing truncated forms of the protein that express the LHN domain and a fragment of the Hc domain. Proteins made according to the method of the invention are useful, for example, as immunodiagnostic agents and vaccine components.

Abstract: The invention provides nitrilases and methods for making and using them, and in one aspect, provides methods for producing enantiomerically pure ?-substituted carboxylic acids, such as, for example, ?-amino acids and ?-hydroxy acids. In one aspect, methods of the invention combine an aldehyde or ketone with a cyanide and ammonia or an ammonium salt or an amine, in the presence of a nitrilase or a polypeptide having nitrilase activity, to stereoselectively hydrolyze the amino nitrile or cyanohydrin intermediate under conditions sufficient to produce the carboxylic acid.

Abstract: The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.

Abstract: A method for expressing and industrial scale production of recombinant lysosomal enzymes utilizing insect larva including the steps of infecting an insect larva population of the species Spodoptera littoralis via a recombinant baculovirus liquid suspension which permits the expression of at least one gene coding for a protein of interest, at least one of these genes coding for a lysosomal enzyme expressed in the insect larva, collecting of the previously infected insect larva expressing in a sufficient significant quantity the protein of interest and recovering the protein of interest from the collected insect larva.

Abstract: The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: The present invention is based, in part, on our discovery of compositions and methods that can be used to systemically deplete arginine and thereby treat arginine-dependent cancers. Our studies indicate that administering a composition that depletes arginine directly to the patient's small intestine will provide effective treatment for arginine-dependent cancers. Moreover, the methods can be carried out in such a way that various sources of arginine are restricted and side effects are minimized. For example, to deplete arginine, one can not only administer an arginine-depleting enzyme directly to the intestinal lumen but can also inhibit endogenous production of arginine, reduce arginine production by intestinal bacteria and limit arginine intake. To minimize side effects, one can inhibit protein breakdown, which may occur as a compensatory mechanism, provide systemic NO from a nitric oxide donor, provide a pressor peptide, and/or provide prostacycline or an analog thereof.

Abstract: A mutein recombinant adenosine deaminase having any oxidizable cysteine residue replaced by a non-oxidizable amino acid residue is disclosed. Stabilized recombinant adenosine deaminase, polymer conjugates and methods of treatment using the same are also disclosed.

Abstract: The present invention relates to methods and genetically engineered methylotrophic yeast strains for producing glycoproteins with mammalian-like glycosylation. The present invention also relates to vectors useful for generating methylotrophic yeast strains capable of producing glycoproteins with mammalian-like glycosylation. Glycoproteins produced from the genetically engineered methylotrophic yeast strains are also provided.

Abstract: The present invention provides methods of detecting cancer using biomarkers.

Abstract: The present invention relates to a mutant prokaryotic penicillin G acylase derived from a wild-type penicillin G acylase characterized in that the mutant is having an amino acid substitution at one or more amino acid positions selected from the group consisting of amino acid positions A3, A77, A90, A144 A192, B24, B109, B148, B313, B460 and B488 according to the amino acid numbering of the Escherichia coli penicillin G acylase having the amino acid sequence depicted in SEQ ID No: 1.

Abstract: The present invention provides a L-succinylacylase consisting of: (a) a protein coded by a gene consisting of a nucleic acid sequence shown in SEQ ID No: 1; (b) a protein consisting of an amino acid sequence shown in SEQ ID No: 2; (c) a protein coded by a polynucleotide which hybridizes under a stringent condition with a nucleic acid sequence which is complementary to the nucleic acid sequence shown in SEQ ID No: 1 and having an L-succinylaminoacylase activity; or (d) a protein which consists of an amino acid sequence where one or several amino acid(s) is/are substituted, deleted, inserted and/or added in the protein consisting of the amino acid sequence shown in SEQ ID No: 2 and has an L-succinylaminoacylase activity. This enzyme is able to produce a sterically bulky unnatural amino acid such as L-tert-leucine etc. which is useful as an intermediate for pharmaceuticals.

Abstract: The application discloses new biomarkers for hypertensive disorders of pregnancy and particularly preeclampsia; methods for the diagnosis, prediction, prognosis and/or monitoring said disorders based on measuring said biomarkers; and kits and devices for measuring said biomarker and/or performing said methods.

Abstract: This disclosure provides modified cytosine deaminases (CDs). The disclosure further relates to cells and vector expressing or comprising such modified CDs and methods of using such modified CDs in the treatment of disease and disorders.

Abstract: The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.

Abstract: The present Invention relates to new nitrilases with modified Substrate acceptance, the method to obtain them and the use of the aforesaid nitrilases. Said nitrilases are encoded by a polypeptide sequence, which at a Position corresponding to Position 296 in wild-type Alcaligenes faecalis comprises an amino acid which is not tyrosine. The Invention further relates to nucleic acid sequences and amino acid sequences encoding Said nitrilases, expression constructs comprising Said nucleic acid sequences, vectors comprising the nucleic acid sequences or the exPression constructs, to organisms, preferably microorganisms, comprising the nucleic acid sequences, expression constructs or vectors. The Invention additionally relates to a method for preparing carboxylic acids, preferably substituted chiral carboxylic acids from racemic nitriles.

Abstract: The document provides modified cytosine deaminases with increased solubility and high levels of DNA cytosine deaminase activity.

Abstract: A high throughput RNAi-based assay for identify factors involved in maintaining epigenetic silencing is disclosed. The assay measures reactivation of a silent reporter gene in cells, resulting from RNAi-based knockdown in target mRNA. RNAi-based screening of these silent reporter cells has identified known enzymes that place or remove epigenetic marks on histones, as well as non-enzymatic proteins that function in silencing or in transfer of marks during S-phase. In addition, the screen has been used to identify a number of novel gene products involved in epigenetic silencing, which are also disclosed.

Abstract: The invention provides methods and compositions for modulating the life span of eukaryotic and prokaryotic cells and for protecting cells against certain stresses, e.g., heatshock. One method comprises modulating the flux of the NAD+ salvage pathway in the cell, e.g., by modulating the level or activity of one or more proteins selected from the group consisting of NPT1, PNC1, NMA1 and NMA2. Another method comprises modulating the level of nicotinamide in the cell.

Abstract: An object is to provide a novel method of improving an enzyme capable of deamidating a protein.

Abstract: Demethylation of a methylated DNA sequence in a eukaryotic cell is described, utilising a molecule that includes at least a first domain that exhibits a cytidine deaminase activity and at least a second domain that confers either a specific or non-specific DNA binding activity. The molecules of the invention are useful in somatic cell nuclear transfer and also in cancer therapy.

Abstract: The present invention features a novel protein engineering strategy by combining the domains of two independent proteins into a molecular switch. The invention features polypeptides comprising a prodrug activating enzyme and a protein that binds a cancer specific marker, polynucleotides encoding the polypeptides, and molecular switches for converting a prodrug into a toxin, comprising the polypeptides. The invention also features methods for converting a prodrug into a toxin, methods for treating cancer, and methods for making the molecular switches, as well as kits.

Abstract: The present invention describes an assay method comprising: (A) generating (1) at least a first fragment of a reporter molecule linked to a first interacting domain and at least a second fragment of a reporter molecule linked to a second interacting domain, or (2) nucleic acid molecules that code for (A)(1) and subsequently allowing said nucleic acid molecules to produce their coded products; then, (B) allowing interaction of said domains; and (C) detecting reconstituted reporter molecule activity, where said reporter molecule can react with a penicillin- or a cephalosporin-class substrate.

Abstract: The invention relates to APOBEC4 proteins and N- or C-terminally modified APOBEC4 proteins for the modulation of the release of retroviruses or viral particles thereof from cells and various uses thereof. Expression of APOBEC4 or N-terminally stabilized APOBEC4 protein in a cell leads to an increased viral production, while expression of C-terminally modified APOBEC4 protein leads to a decrease in viral production.