Acting On A Linear Amide Linkage In Linear Amide Patents (Class 435/228)
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Patent number: 6352848Abstract: A novel rec-L-N-carbamoylase from Arthrobacter aurescens and its method of use for producing L-amino acids. The recombinantly produced L-carbamoylase is unexpectedly stable, so that an industrial method of producing L-amino acids can be established with it, in contrast to previously known L-carbamoylases.Type: GrantFiled: April 2, 1999Date of Patent: March 5, 2002Assignees: Degussa-Huls Aktiengesellschaft, Universitat Stuttgart, Roche Diagnostics GmbHInventors: Josef Altenbuchner, Ralf Mattes, Markus Pietzsch, Christoph Syldatk, Anja Wiese, Burkard Wilms
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Patent number: 6287828Abstract: A process for the bioconversion of a nitrile to its corresponding amide product, particularly acrylonitrile to acrylamide which is used for forming polymers. The process uses a thermophilic bacterium having a nitrile hydratase activity that is constitutively expressed, activated by cobalt ions, stable at 60° C., and is most active between 20° C. to 70° C. with optimum activity at 55° C. Alternatively, the process uses the enzyme extracted from the thermophilic bacterium to convert a nitrile to its amide product. The genes encoding nitrile hydratase and amidase are described in which the former is useful for the conversion of an nitrile to its amide and the later is useful for the conversion of an amide to its acid.Type: GrantFiled: April 14, 2000Date of Patent: September 11, 2001Assignee: Board of Trustees operating Michigan State UniversityInventors: Patrick J. Oriel, Rugmini Padmakumar, Sang Hoon Kim
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Patent number: 6271015Abstract: The soporific activity of cis-9,10-octadecenoamide and other soporific fatty acid primary(amides is neutralized by hydrolysis in the presence of fatty-acid amide hydrolase (FAAH). Hydrolysis of cis-9,10-octadecenoamide by FAAH leads to the formation of oleic acid, a compound without soporific activity. FAAH has be isolated and the gene encoding FAAH has been cloned, sequenced, and used to express recombinant FAAH. Inhibitors of FAAH are disclosed to block the hydrolase activity.Type: GrantFiled: November 4, 1996Date of Patent: August 7, 2001Assignee: The Scripps Research InstituteInventors: Norton B. Gilula, Benjamin F. Cravatt, Richard A. Lerner
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Patent number: 6251651Abstract: A novel enzyme which has an activity to release side chain carboxyl groups and ammonia from a protein by acting upon side chain amido groups in the protein. This invention relates to a method for the production of an enzyme, which comprises culturing in a medium a strain that belongs to a bacterium classified into Cytophagales or Actinomycetes and has the ability to produce an enzyme having a property to deamidate amido groups in protein, thereby effecting production of said enzyme, and subsequently collecting said enzyme from the culture mixture. It also relates to a method for the modification of protein making use of a novel enzyme which directly acts upon amido groups in protein as well as to an enzyme which has a property to deamidate amido groups in protein and a gene which encodes said enzyme.Type: GrantFiled: June 3, 1999Date of Patent: June 26, 2001Assignee: Amano Pharmaceutical Co., Ltd.Inventors: Shotaro Yamaguchi, Akira Matsuura
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Patent number: 6248551Abstract: This invention relates to Helicobacter species aliphatic amidase AmiE polypeptides, the DNA encoding those polypeptides and transformed microorganisms capable of expressing those polypeptides. This invention also relates to the use of Helicobacter sp. (particularly Helicobacter pylori) amidase AmiE polypeptides and antibodies specific for those polypeptides in immunogenic, therapeutic, and diagnostic applications. The invention additionally relates to processes of producing Helicobacter species aliphatic amidase AmiE polypeptides and intermediates useful in the production of those polypeptides.Type: GrantFiled: February 23, 1998Date of Patent: June 19, 2001Assignee: Institut PasteurInventors: Hilde De Reuse, Stephane Skouloubris, Agnes Labigne
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Patent number: 6235516Abstract: The invention belongs to the field of biotechnology. It concerns a biocatalyst, i.e. a dead or living microorganism or a polypeptide, preferably in isolated form, which exhibits acylase enzymatic activity without lipase- or esterase-activity. The biocatalyst is capable of stereoselectively hydrolysing a racemic acylamide which has an aliphatic acyl residue and which is not a derivative of a natural amino acid.Type: GrantFiled: November 12, 1998Date of Patent: May 22, 2001Assignee: Novartis AGInventors: Oreste Ghisalba, Matthias Kittelmann, Kurt Laumen, Paula Walser-Volken
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Patent number: 6214592Abstract: The present invention relates to an enzyme with amidase activity, particularly towards substrates of the oligomer type derived from PA 6.Type: GrantFiled: April 3, 1998Date of Patent: April 10, 2001Assignee: Rhone-Poulenc Fibres et Polymeres S.A.Inventors: Joël Crouzet, Olivier Favre-Bulle, Catherine Jourdat, Anne-Marie Le Coq, Dominique Petre
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Patent number: 6180388Abstract: The present invention relates to a process for the enzymatic hydrolysis of polyamides 6.6 to give adipic acid monomers and hexamethylenediamine monomers. The present invention further relates to an enzyme with amidase activity particularly towards substrates of the oligomer type derived from PA 6.6 and/or PA 6, said enzyme being characterized in that it consists of a peptide sequence corresponding to SEQ ID NO: 1 in the attached sequence listing and/or at least one polypeptide homologous to this sequence. The invention further relates to the DNA coding for said enzyme and to the biological precursors thereof The invention further relates to the microorganisms capable of producing this enzyme and to the hydrolysis process in which this enzyme and/or these microorganisms are applied.Type: GrantFiled: April 3, 1998Date of Patent: January 30, 2001Assignee: Rhone-Poulenc Fibres et Polymeres S.A.Inventors: Jo{umlaut over (e)}l Crouzet, Didier Faucher, Olivier Favre-Bulle, Catherine Jourdat, Dominique Petre, J{acute over (e)}r{circumflex over (o)}me Pierrard, Denis Thibaut, Carole Guitton
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Patent number: 6156555Abstract: A purified enzyme-I is obtained that participates in C-terminal amidation by acting on a peptide C-terminal glycine adduct to form a peptide C-terminal .alpha.-hydroxyglycine adduct. The enzyme has an optimum pH of about 5 to 7, an optimum temperature of 25 to 40.degree. C. and a molecular weight of about 25 kDa or about 36 kDa, and metal ions and ascorbic acid act as a cofactor. A purified enzyme-II is obtained that participates in C-terminal amidation by acting on the peptide C-terminal .alpha.-hydroxyglycine adduct to produce a C-terminal amidated compound. The enzyme has an optimum pH of about 5 to 6, an optimum temperature of 15 to 35.degree. C. and a molecular weight of about 40 kDa or about 43 kDa. Enzyme-I does not act on the peptide C-terminal .alpha.-hydroxyglycine adduct and enzyme-II does not act on the peptide C-terminal glycine adduct. The enzymes may be purified from a biological material such as horse serum by affinity chromatography using a peptide C-terminal glycine adduct as a ligand.Type: GrantFiled: October 14, 1998Date of Patent: December 5, 2000Assignee: Shiseido Company Ltd.Inventors: Toshii Iida, Toshihiko Kaminuma, Yuka Fuse, Masahiro Tajima, Mitsuo Yanagi, Hiroshi Okamoto, Jiro Kishimoto, Ohji Ifuku, Ichiro Kato
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Patent number: 6146872Abstract: The present invention provides a cyclic lipopeptide acylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.Type: GrantFiled: December 31, 1998Date of Patent: November 14, 2000Assignee: Fukisawa Pharmaceutical Co., Ltd.Inventors: Satoshi Ueda, Miho Tanaka, Masami Ezaki, Kazutoshi Sakamoto, Seiji Hashimoto, Nobutaka Oohata, Masaru Tsuboi, Michio Yamashita
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Patent number: 6146871Abstract: A procedure for producing a modified 7.beta.-(4-carboxybutanamide) cephalosporinase enzyme which can be purified in a single chromatographic step. The procedure for production of the enzyme involves: mutagenizing the gene which codes for the enzyme from Acinetobacter sp. ATCC 53891 by inserting a nucleotide sequence coding for six histidine residues; fusing the mutant gene with high-efficiency promoter DNA sequences; transforming Escherichia coli cells with the fusion gene construct; growing the transformed Escherichia coli cells; and recovering the enzyme by the use of supports which contain metal chelates. 7-Aminocephalosporanic acid is an important intermediate for the manufacture of a wide range of antibacterial agents of the cephalosporin family.Type: GrantFiled: August 13, 1998Date of Patent: November 14, 2000Assignee: Sntibioticos, S. A.Inventors: Jose Luis Garcia Lopez, Estrella Cortes Rubio, Jose Manuel Guisan Seijas, Jose Luis Barredo Fuente, Bruno Diez Garcia, Alfonso Collados de la Vieja, Alejandro Vitaller Alba, Francisco Salto Maldonado
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Patent number: 6136583Abstract: A purified thermostable enzyme is derived from the archael bacterium Thermococcus GU5L5. The enzyme has a molecular weight of about 68.5 kilodaltons and has cellulase activity. The enzyme can be produced from native or recombinant host cells and can be used for the removal of arginine, phenylalanine, or methionine amino acids from the N-terminal end of peptides in peptide or peptidomimetic synthesis. The enzyme is selective for the L, or `natural` enantiomer of the amino acid derivatives and is therefore useful for the production of optically active compounds. These reactions can be performed in the presence of the chemically more reactive ester functionality, a step which is very difficult to achieve with nonenzymatic methods.Type: GrantFiled: October 15, 1997Date of Patent: October 24, 2000Assignee: Diversa CorporationInventors: Dennis Murphy, John Reid, Dan Robertson
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Patent number: 6083917Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian protein farnesyltransferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. One protein farnesyltransferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. Also disclosed are methods and compositions for the preparation of farnesyltransferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras.Type: GrantFiled: August 24, 1992Date of Patent: July 4, 2000Assignee: Board of Regents, The University of Texas SystemInventors: Michael S. Brown, Joseph L. Goldstein, Yuval Reiss, Jim Marsters
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Patent number: 6063409Abstract: A microorganism belonging to the genus Cryptococcus having the ability to produce glutaminase excellent in salt resistance and thermostability. Further, this microorganism can be used to produce the salt-resistant thermostable glutaminase, and by use of this glutaminase, glutamic acid-rich and good tasting protein hydrolysates (e.g. flavoring foods such as soy sauce, miso etc.) are produced efficiently in a simple operation. Specifically, said microorganism is the new species Cryptococcus nodaensis having assimilability of +, -, -and - toward lactose, N-acetyl-D-glucosamine, D-glucosamine and arbtin as carbon sources, respectively.Type: GrantFiled: December 14, 1998Date of Patent: May 16, 2000Assignee: Kikkoman CorporationInventors: Itsuo Sato, Hiroe Sato, Yoshiki Hanya, Keietsu Abe, Mitsuharu Fujii, Tadanobu Nakadai, Jack W. Fell
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Patent number: 6030823Abstract: A novel D-aminoacylase was derived from a microorganism belonging to the genus Sebekia. This enzyme is useful for producing D-amino acids from N-acetyl-DL-amino acids on an industrial scale.Type: GrantFiled: March 16, 1999Date of Patent: February 29, 2000Assignee: Daicel Chemical Industries, Ltd.Inventor: Shinji Tokuyama
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Patent number: 6004796Abstract: A purified thermostable enzyme is derived from the archael bacterium Thermococcus GU5L5. The enzyme has a molecular weight of about 68.5 kilodaltons and has cellulase activity. The enzyme can be produced from native or recombinant host cells and can be used for the removal of arginine, phenylalanine, or methionine amino acids from the N-terminal end of peptides in peptide or peptidomimetic synthesis. The enzyme is selective for the L, or `natural` enantiomer of the amino acid derivatives and is therefore useful for the production of optically active compounds. These reactions can be performed in the presence of the chemically more reactive ester functionality, a step which is very difficult to achieve with nonenzymatic methods.Type: GrantFiled: March 2, 1999Date of Patent: December 21, 1999Assignee: Diversa CorporationInventors: Dennis Murphy, John Reid, Dan Robertson
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Patent number: 5998194Abstract: The present invention provides isolated polynucleotides from Saccharomyces erythraea that encode enzymes involved in the biosynthesis of polyketide-associated sugars. Methods of using the polynucleotides to produce novel glycosylation modified polyketides are also provided.Type: GrantFiled: December 21, 1995Date of Patent: December 7, 1999Assignee: Abbott LaboratoriesInventors: Richard G. Summers, Jr., Leonard Katz, Stefano Donadio, Michael J. Staver
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Patent number: 5985646Abstract: A purified thermostable enzyme is derived from the archael bacterium Thermococcus GU5L5. The enzyme has a molecular weight of about 68.5 kilodaltons and has cellulase activity. The enzyme can be produced from native or recombinant host cells and can be used for the removal of arginine, phenylalanine, or methionine amino acids from the N-terminal end of peptides in peptide or peptidomimetic synthesis. The enzyme is selective for the L, or `natural` enantiomer of the amino acid derivatives and is therefore useful for the production of optically active compounds. These reactions can be performed in the presence of the chemically more reactive ester functionality, a step which is very difficult to achieve with nonenzymatic methods.Type: GrantFiled: April 24, 1998Date of Patent: November 16, 1999Assignee: Diversa CorporationInventors: Dennis Murphy, John Reid, Dan Robertson
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Patent number: 5985631Abstract: A method for preventing the activation of inactive, recombinant Helicobacter pylori apourease is presented. The method comprises contacting the apourease with a compound that modifies a sulfhydryl or lysyl residue of the urease. The covalently modified apourease is prevented from molecular aggregation.Type: GrantFiled: September 12, 1997Date of Patent: November 16, 1999Assignee: OraVax-Merieux Co.Inventors: Gopalan Soman, William D. Thomas, Jr., Thomas P. Monath
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Patent number: 5962284Abstract: Acrylamidase enzymes are provided which have acrylamidase activity at pH 4.0 which is at least 50% of their acrylamidase activity at pH 7.0. Such enzymes can be produced by the novel microorganisms Rhodococcus strains NCIMB 40889 and NCIMB 40755. Such enzymes and microorganisms can be used for reducing free acrylamide in polyacrylamides which are produced at low pH and in particular cationic and substantially non-ionic polyacrylamides.Type: GrantFiled: August 7, 1998Date of Patent: October 5, 1999Assignee: Ciba Specialty Chemicals Water Treatments LimitedInventors: Jonathan Hughes, Yvonne Christine Armitage
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Patent number: 5936074Abstract: The present invention is directed to deacyl teicoplanin, and to a process for preparing deacyl teicoplanin by reacting teicoplanin with ECB deacylase. Deacyl teicoplanin can be alkylated to produce compounds useful for their antibacterial activity.Type: GrantFiled: April 1, 1998Date of Patent: August 10, 1999Assignee: Eli Lilly and CompanyInventors: Barbara Shreve Briggs, Robin David Grey Cooper, Adam Joseph Kreuzman, Milton Joseph Zmijewski, Jr.
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Patent number: 5935831Abstract: New mutant .beta.-lactam acylases are provided exhibiting altered substrate specificities. These .beta.-lactam acylases are obtained by expression of a gene encoding said .beta.-lactam acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type .beta.-lactam acylase.Type: GrantFiled: October 10, 1995Date of Patent: August 10, 1999Assignee: Gist-Brocades, N.V.Inventors: Wilhelmus Johannes Quax, Onno Misset, Jan Metske Van Der Laan, Herman B. M. Lenting
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Patent number: 5888785Abstract: The present invention provides a nitrile hydratase nucleic acid fragment isolated from Pseudomonas putida which encodes a nitrile hydratase activity capable of catalyzing the hydrolysis of certain racemic nitrites to the corresponding R- or S-amides. Also provided are transformed microorganisms capable of the active expression of said nitrile hydratase activity. Additionally, the invention provides a transformant harboring the nitrile hydratase gene in conjunction with an amidase gene, both of which may be co-expressed producing active nitrile hydratase and amidase enzymes respectively. Methods for the production of such enantiomeric materials are also provided.Type: GrantFiled: June 24, 1998Date of Patent: March 30, 1999Assignee: E. I. du Pont de Nemours and CompanyInventors: Robert Donald Fallon, Mark James Nelson, Mark Scott Payne
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Patent number: 5877002Abstract: The present invention relates to thermostable mutants of Agrobacterium radiobacter D-N-.alpha.-carbamoylase and means and methods for their preparation. The thermostable mutants have an unaltered or improved activity with respect to the wild-type enzyme and are particularly useful in the preparation of D-.alpha.-amino acids.Type: GrantFiled: December 9, 1996Date of Patent: March 2, 1999Assignee: Eniricerche S.p.A.Inventors: Renata Grifantini, Giovanna Carpani, Giuliano Galli, Guido Grandi
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Patent number: 5877003Abstract: The present invention relates to thermostable mutants of D-N-.alpha.-carbamoylase and means and methods for their preparation. The thermostable mutants have an unaltered or improved activity with respect to the wild-type enzyme and are particularly useful in the preparation of D-.alpha.-amino acids.Type: GrantFiled: December 30, 1997Date of Patent: March 2, 1999Assignee: Eniricerche S.p.AInventors: Renata Grifantini, Giovanna Carpani, Giuliano Galli, Guido Grandi
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Patent number: 5877001Abstract: A purified thermostable enzyme is derived from the archael bacterium Thermococcus GU5L5. The enzyme has a molecular weight of about 68.5 kilodaltons and has cellulase activity. The enzyme can be produced from native or recombinant host cells and can be used for the removal of arginine, phenylalanine, or methionine amino acids from the N-terminal end of peptides in peptide or peptidomimetic synthesis. The enzyme is selective for the L, or `natural` enantiomer of the amino acid derivatives and is therefore useful for the production of optically active compounds. These reactions can be performed in the presence of the chemically more reactive ester functionality, a step which is very difficult to achieve with nonenzymatic methods.Type: GrantFiled: June 17, 1996Date of Patent: March 2, 1999Assignee: Diverso CorporationInventors: Dennis Murphy, John Reid, Dan Robertson
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Patent number: 5871995Abstract: A purified enzyme-I is obtained that participates in C-terminal amidation by acting on a peptide C-terminal glycine adduct to form a peptide C-terminal .alpha.-hydroxyglycine adduct. The enzyme has an optimum pH of about 5 to 7, an optimum temperature of 25.degree. to 40.degree. C. and a molecular weight of about 25 kDa or about 36 kDa, and metal ions and ascorbic acid act as a cofactor. A purified enzyme-II is obtained that participates in C-terminal amidation by acting on a peptide C-terminal .alpha.-hydroxyglycine adduct to produce a C-terminal amidated compound. The enzyme has an optimum pH of about 5 to 6, an optimum temperature of 15.degree. to 35.degree. C. and a molecular weight of about 40 kDa or about 43 kDa. Enzyme-I does not act on the peptide C-terminal .alpha.-hydroxyglycine adduct and enzyme-II does not act on the peptide C-terminal glycine adduct.Type: GrantFiled: May 24, 1991Date of Patent: February 16, 1999Assignee: Shiseido Company, Ltd.Inventors: Toshii Iida, Toshihiko Kaminuma, Yuka Fuse, Masahiro Tajima, Mitsuo Yanagi, Hiroshi Okamoto, Jiro Kishimoto, Ohji Ifuku, Ichiro Kato
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Patent number: 5869299Abstract: A process for preparing clavulanic acid and other clavam derivatives using an enzyme system from Streptomyces, particularly S. Clavuligerus.Type: GrantFiled: August 25, 1995Date of Patent: February 9, 1999Assignee: SmithKline Beecham p.l.c.Inventors: Keith Howard Baggaley, Neville Hubert Nicholson, Stephen William Elson, Jeffrey Edwards, Alison Jane Earl, William Henry Holms, David Michael Mousdale, Jack Edward Baldwin, Christopher Schofield
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Patent number: 5863785Abstract: In a process for the production of a D-.alpha.-amino acid, in which an N-carbamyl-D-.alpha.-amino acid corresponding to the general formula: ##STR1## wherein R represents phenyl, hydroxy-substituted phenyl, substituted or unsubstituted alkyl, or thienyl, is converted by a microbial enzyme in an aqueous medium to a D-.alpha.-amino acid corresponding to the general formula: ##STR2## wherein R is the same as defined above, decarbamylase produced by a microorganism of the genus Comamonas, Blastobacter, Alcaligenes, Sporosarcina, Rhizobium, Bradyrhizobium or Arthrobacter is used as the enzyme converting the N-carbamyl-D-.alpha.-amino acid to the D-.alpha.-amino acid.The conversion of the N-carbamyl-D-.alpha.-amino acids to the D-.alpha.-amino acids is carried out in a neutral to alkaline pH range.Type: GrantFiled: June 7, 1995Date of Patent: January 26, 1999Assignee: Kanegafuchi Chemical Industry Co., Ltd.Inventors: Hideaki Yamada, Sakayu Shimizu, Yasuhiro Ikenaka, Kazuyoshi Yajima, Yukio Yamada, Hirokazu Nanba, Masayuki Takano, Satomi Takahashi
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Patent number: 5854051Abstract: The present invention relates to: parasitic helminth asparaginase proteins; parasitic helminth asparaginase nucleic acid molecules, including those that encode such asparaginase proteins; antibodies raised against such asparaginase proteins; and compounds that inhibit parasitic helminth asparaginase activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to protect animals from diseases caused by parasitic helminths.Type: GrantFiled: September 15, 1997Date of Patent: December 29, 1998Assignees: Heska Corporation, Colorado State University Research FoundationInventors: Ramaswamy Chandrashekar, Naotoshi Tsuji
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Patent number: 5834243Abstract: A method for producing recombinant peptides and proteins having a diminished retention of N-formyl-methionine by coexpressing a peptide deformylase enzyme is disclosed. Also disclosed are substantially deformylated protein compositions and transformed bacterial cells and DNA vectors useful for acheiving such deformylation.Type: GrantFiled: July 17, 1997Date of Patent: November 10, 1998Inventor: Gregg Bogosian
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Patent number: 5824522Abstract: Decarbamylases are provided capable of producing D-.alpha.-amino acids by hydrolysis of N-carbamyl-D-.alpha.-amino acids. A source of the decarbamylases is recombinant microorganisms produced by gene manipulation methods. Decarbamylases having improved thermostability can be obtained in which amino acids at a thermostability-related site of a natural decarbamylase have been replaced with other amino acids by mutating a DNA fragment encoding the natural decarbamylase. Recombinant DNA is obtained from a vector DNA and a DNA fragment encoding a natural decarbamylase where the nucleic acid sequence encoding an amino acid at a thermostability-related site is replaced with a nucleic acid sequence encoding another amino acid. The recombinant DNA is used to produce transformants that produce thermostable decarbamylases.Type: GrantFiled: August 22, 1994Date of Patent: October 20, 1998Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Yasuhiro Ikenaka, Hirokazu Nanba, Masayuki Takano, Kazuyoshi Yajima, Yukio Yamada, Satomi Takahashi, Kazuma Okubo, Kazuhiko Yamada, Yoshiro Hiraishi
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Patent number: 5811286Abstract: The present invention provides a nitrile hydratase nucleic acid fragment isolated from Pseudomonas putida which encodes a nitrile hydratase activity capable of catalyzing the hydrolysis of certain racemic nitriles to the corresponding R- or S-amides. Also provided are transformed microorganisms capable of the active expression of said nitrile hydratase activity. Additionally, the invention provides a transformant harboring the nitrile hydratase gene in conjunction with an amidase gene, both of which may be co-expressed producing active nitrile hydratase and amidase enzymes respectively. Methods for the production of such enantiomeric materials are also provided.Type: GrantFiled: October 4, 1996Date of Patent: September 22, 1998Assignee: E. I. du Pont de Nemours and CompanyInventors: Robert Donald Fallon, Mark James Nelson, Mark Scott Payne
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Patent number: 5804429Abstract: A mutant CC acylase wherein at least one amino acid at the Ala.sup.49, Met.sup.164, Ser.sup.166, Met.sup.174, Glu.sup.358, Met.sup.465, Met.sup.506, or Met.sup.750 position of the amino acid sequence of the native CC acylase is replaced by a different amino acid, a DNA coding therefor, an expression vector containing the said DNA, a microorganism transformed with the said expression vector, the production of the CC acylase by culturing the said transformant, and use thereof for the production of a compound. The mutant CC acylase of the invention has desirable properties in terms of enzymatic potency, alteration of pH profile, efficiency of processing, and the like.Type: GrantFiled: May 1, 1996Date of Patent: September 8, 1998Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Mineo Niwa, Yoshimasa Saito, Takao Fujimura, Yoshinori Ishii, Yuji Noguchi
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Patent number: 5795802Abstract: A method for manufacturing a semiconductor device, the method includes the steps of forming an n-type well and a p-type well under a surface of a semiconductor substrate, forming a pad oxide layer having a first thickness on the p-type well and a second thickness on the n-type well, the first thickness being greater than the second thickness, and forming a field oxide layer between the n-type well and the p-type well, the field oxide layer having less bird's beak on the n-type well than on the p-type well.Type: GrantFiled: September 3, 1997Date of Patent: August 18, 1998Assignee: LG Semicon Co., Ltd.Inventors: Sang-Gi Ko, Mun-Mo Jeong
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Patent number: 5773284Abstract: Process for the preparation of a threo-phenylserine amide of the general formula 2 in which glycine amide is contacted with the corresponding substituted benzaldehyde of formula 3 in an excess relative to the amount of glycine amide, this taking place at a pH between 9 and 14 in the presence of a suitable solvent. The resulting phenylserine amide can subsequently be hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently subjected to a stereoselective enzymatic hydrolysis yielding a (2S,3R) phenylserine. The non-hydrolyzed (2R,3S) phenylserine amide can be isolated as a Schiff base and be recirculated and simply racemized. The (2S,3R) phenylserine obtained can be used in the preparation of thiamphenicol or florfenicol. The threo-phenylserine amides of the general formula 1 or 2 are new intermediates in this commercially attractive process for the preparation of thiamphenicol and florfenicol.Type: GrantFiled: June 12, 1996Date of Patent: June 30, 1998Assignee: DSM N.V.Inventor: Bernardus Kaptein
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Patent number: 5766918Abstract: The present invention concerns polypeptides that possess an enantioselective amidase activity. It also concerns the genetic material required for the expression of these polypeptides as well as a microbiological procedure for their preparation. Finally, this invention concerns the utilization of these polypeptides and of transformed microorganisms for the enantioselective synthesis of acids from racemic amides, and in particular propionic acids, especially (S)-2-aryl-propionamide.Type: GrantFiled: October 5, 1995Date of Patent: June 16, 1998Assignee: Rhone-Poulenc SanteInventors: Dominique Petre, Edith Cerbelaud, Jean-Fran.cedilla.ois Mayaux, Patrice Yeh
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Patent number: 5766871Abstract: A method of screening for a given enzyme in colony-forming cells using a substrate of the enzyme that has low solubility. Use of such a method leads to the discovery of glutaryl-7-aminocephalosporanic acid (GL-7-ACA) acylase of Pseudomonas nitroreducens. Also disclosed is a method of obtaining GL-7-ACA acylase from Pseudomonas cells.Type: GrantFiled: November 27, 1996Date of Patent: June 16, 1998Assignee: Food Industry Research and Development InstituteInventors: Wen-Shen Chu, Yun-Huey Lee, Ming-Chu Chen, Li-Lin Chen, Chiou-Yen Wen
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Patent number: 5744325Abstract: A process for producing N-acetylglucosamine-6-phosphate deacetylase comprising incubating a microorganism which belongs to the marine psychrotrophic bacterium Vibrio sp. and recovering the N-acetylglucosamine-6-phosphate deacetylase from the culture thus obtained; N-acetylglucosamine-6-phosphate deacetylase; and a bacterium belonging to the marine psychrotrophic bacterium Vibrio sp.Type: GrantFiled: February 26, 1997Date of Patent: April 28, 1998Assignee: Agency of Industrial Science and TechnologyInventors: Shizu Fujishima, Naoko Yamano, Akihiko Maruyama, Takanori Higashihara
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Patent number: 5702939Abstract: A glucosamine 6-phosphate deaminase having specific physicochemical properties. A process for producing the glucosamine 6-phosphate deaminase which comprises incubating a microorganism belonging to the genus Vibrio and harvesting the glucosamine 6-phosphate deaminase from the culture thus obtained.Type: GrantFiled: March 7, 1996Date of Patent: December 30, 1997Assignee: Agency of Industrial Science & TechnologyInventors: Shizu Fujishima, Naoko Yamano
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Patent number: 5695968Abstract: The present invention is directed to a gene which is related to a D-N-carbamoyl-.alpha.-amino acid amidohydrolase which is an enzyme capable of converting D-N-carbamoyl-.alpha.-amino acids into D-.alpha.-amino acids; a recombinant plasmid in which a DNA fragment containing the gene is incorporated into a vector; a microorganism belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Corynebacterium, or Brevibacterium, which is transformed by incorporating the recombinant plasmid thereinto; a process for the production of D-N-carbamoyl-.alpha.-amino acid amidohydrolases, comprising the steps of cultivating the transformed microorganism and collecting the desired product therefrom; a D-N-carbamoyl-.alpha.-amino acid amidohydrolase obtained by the method; and a process for the production of D-.alpha.-amino acids with the aid of an action of the enzyme.The D-N-carbamoyl-.alpha.-amino acid amidohydrolase can be fixed on a support for immobilization and used as an immobilized enzyme.Type: GrantFiled: June 7, 1995Date of Patent: December 9, 1997Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Hirokazu Nanba, Yukio Yamada, Masayuki Takano, Yasuhiro Ikenaka, Satomi Takahashi, Kazuyoshi Yajima
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Patent number: 5658755Abstract: Heterologous extra-cellular expression of recombinant proteins in soluble functional form is desirable because of the ease associated with purification of the secreted proteins and avoidance of the need for cell extraction and protein refolding procedures. The present invention provides DNA sequences of the naturally-occurring phthalyl amidase gene isolated from Xanthobacter agilis that control transcription, translation, and extra-cellular secretion of proteins in Streptomyces lividans. These DNA sequences can be used in a method for extra-cellular expression of a wide variety of proteins in soluble functional form.Type: GrantFiled: July 15, 1994Date of Patent: August 19, 1997Assignee: Eli Lilly and CompanyInventors: Stephen W. Queener, Joseph M. Zock
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Patent number: 5635379Abstract: Peptides containing in its amino acid chain a D-2-alkylTryptophan residue wherein the alkyl group has between one and three carbon atoms and having pharmacological activity similar to that of analogous peptides containing natural unsubstituted D-Tryptophan residues in place of the D-2-alkylTryptophan. These new peptides are more resistant to oxidative degradation which usually takes place, for example, in the presence of reactive radicals or during high energy sterilization than unsubstituted Tryptophan containing peptides. Specific peptides include His-D-2-alkyl-Trp-Ala-Trp-D-Phe-Lys-NH.sub.2, Ala-His-D-2-alkyl-Trp-Ala-Trp-D-Phe-Lys-NH.sub.2, Pyro-Glu-His-Trp-Ser-Tyr-D-2-alkyl-Trp-Leu-Arg-Pro-Gly-NH.sub.2, Pyro-Glu-His-Ser-Tyr-D-2-alkyl-Trp-Leu-Arg-Pro-NHCH.sub.2 CH.sub.3, D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-2-alkyl-Trp-Met-NH.sub.2, Arg-D-Trp-N-methyl-Phe-D-2-alkyl-Trp-Leu-Met-NH.sub.2, D-Phe-Cys-Phe-D-2-alkyl-Trp-Lys-Thr-Cys-NHCH(CH.sub.2 OH)CHOHCH.sub.3 and D-Phe-Cys-Tyr-D-2-alkyl-Trp-Lys-Val-Cys-Trp-NH.sub.2.Type: GrantFiled: October 30, 1995Date of Patent: June 3, 1997Assignee: Romano DeghenghiInventor: Romano Deghenghi
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Patent number: 5627065Abstract: A DNA fragment that contains a gene encoding creatinine amidohydrolase is provided. This invention also provides a recombinant vector containing the said DNA fragment, a transformant containing the said vector, and a method for producing creatinine amidohydrolase by the use of the said transformant.Type: GrantFiled: June 29, 1992Date of Patent: May 6, 1997Assignee: Toyo Boseki Kabushiki KaishaInventors: Kazumi Yamamoto, Masanori Oka, Toshiro Kikuchi, Shigenori Emi
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Patent number: 5612210Abstract: The present invention relates to a process for producing large amounts of 7.beta.-(4-carboxybutanamido)-cephalosporanic acid acylase ("GA") enzyme, which process consists in growing, under suitable culture conditions, a recombinant Escherichia coli K12 strain and subsequently extracting the enzyme from the resulting culture.Enzyme production is controlled by a particular expression system which can be induced by corn-steep liquor, an extremely low cost component of the culture medium.The enzyme can be used in the enzymatic preparation of 7-amino-cephalosporanic acid by starting from 7.beta.-(4-carboxybutanamido)-cephalosporanic acid.Type: GrantFiled: December 30, 1994Date of Patent: March 18, 1997Assignee: Ministero Dell'Universita' e Della Ricerca Scientifica e TecnologicaInventors: Wilhelmus Van der Goes, Antonella Bernardi, Aldo Bosetti, Pietro Cesti, Giuliana Franzosi
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Patent number: 5607850Abstract: Phthalyl amidase is an enzyme previously unknown in the art that catalyzes removal of the phthalyl moiety from phthalyl-containing amides. The current invention provides said phthalyl amidase, means for producing it by culturing the natural organism from which the activity was identified, and methods for using said phthalyl amidase to remove the phthalyl moiety from phthalyl-containing amides.Type: GrantFiled: May 22, 1995Date of Patent: March 4, 1997Assignee: Eli Lilly and CompanyInventors: Barbara S. Briggs, Milton J. Zmijewski, Jr.
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Patent number: 5594032Abstract: Treatment of erectile dysfunction comprising administering to a patient, inducible Nitric Oxide Synthase (iNOS) agents, including penile iNOS, inducers of penile iNOS, iNOS cDNA, or penile smooth muscle cells transformed with iNOS cDNA. Typical in vivo treatment involves delivery of these agents to the penile tissue of a patient by constant or intermittent implanted or external infusion pump, by implantation of time-release microcapsules or introduction of the genetically-engineered cells as by injection. Also disclosed are methods of treatment involving in vitro induction of iNOS in cultured smooth muscle cells and thereafter delivery of purified or recombinant iNOS enzyme, production of iNOS cDNA and genetic transformation with iNOS cDNA, followed by delivery thereof to the penis of a patient.Type: GrantFiled: November 10, 1994Date of Patent: January 14, 1997Inventors: Nestor F. Gonzalez-Cadavid, Jacob Rajfer
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Patent number: 5573955Abstract: A method for reducing or eliminating tyramine interference from amphetamine and methamphetamine immunoassays, comprising treating the sample with aqueous tyramine oxidase for a time and at a temperature and pH sufficient to deaminate any tyramine present in the sample, is provided.Type: GrantFiled: June 5, 1995Date of Patent: November 12, 1996Assignee: Microgenics Corp.Inventors: Pyare Khanna, Theresa Medlin
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Patent number: 5565344Abstract: The present invention is directed to a gene which is related to a D-N-carbamoyl-.alpha.-amino acid amidohydrolase which is an enzyme capable of converting D-N-carbamoyl-.alpha.-amino acids into D-.alpha.-amino acids; a recombinant plasmid in which a DNA fragment containing the gene is incorporated into a vector; a microorganism belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Corynebacterium, or Brevibacterium, which is transformed by incorporating the recombinant plasmid thereinto; a process for the production of D-N-carbamoyl-.alpha.-amino acid amidohydrolases, comprising the steps of cultivating the transformed microorganism and collecting the desired product therefrom; a D-N-carbamoyl-.alpha.-amino acid amidohydrolase obtained by the method; and a process for the production of D-.alpha.-amino acids with the aid of an action of the enzyme.The D-N-carbamoyl-.alpha.-amino acid amidohydrolase can be fixed on a support for immobilization and used as an immobilized enzyme.Type: GrantFiled: August 7, 1992Date of Patent: October 15, 1996Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Hirokazu Nanba, Yukio Yamada, Masayuki Takano, Yasuhiro Ikenaka, Satomi Takahashi, Kazuyoshi Yajima
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Patent number: 5543497Abstract: Phthalyl amidase is an enzyme previously unknown in the art that catalyzes removal of the phthalyl moiety from phthalyl-containing amides. The current invention provides DNA compounds encoding the phthalyl amidase enzyme and methods for expressing such compounds. The present invention also provides recombinant DNA vectors encoding phthalyl amidase and host cells transformed with these DNA vectors.Type: GrantFiled: May 22, 1995Date of Patent: August 6, 1996Assignee: Eli Lilly and CompanyInventors: Stephen W. Queener, Joseph M. Zock