Abstract: This invention provides a process for preparation of trans-4-hydroxy-L-proline which comprises either culturing Xanthomonas maltophilia NA-62 (FERM BP-4479), Xanthomonas maltophilia JCM No.3807 (FERM BP-4474) or Xanthomonas sp. JCM No.3857 (FERM BP-4475) in a nutrient medium containing collagen or gelatin or a partial hydrolyzate of collagen or gelatin, or contacting culture cells of the above microorganism with collagen or gelatin or a partial hydrolyzate of collagen or gelatin in an aqueous medium, and recovering trans-4-hydroxy-L-proline formed; and a process for preparation of an amino acid mixture which comprises contacting culture cells, fractured cells before or after removal of the broken pieces of the cells, or a crude enzyme obtained by subjecting the fractured cells after removal of the broken pieces of the cells to salting-out or solvent precipitation, from Xanthomonas maltophilia NA-62 (FERM BP-4479), Xanthomonas maltophilia JCM No.3807 (FERM BP-4474) or Xanthomonas sp. JCM No.

Abstract: A brandykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.

Abstract: A bradykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.

Abstract: The present invention provides a heterodimeric compound possessing bradykinin and neurokinin receptor antagonist activities useful in the treatment of asthma and other inflammatory diseases especially those involving the airway or pulmonary system. The present invention is also useful in the treatment of pain and inflammation.

Abstract: The treatment of blood and other body fluids and tissues, the detection of tumors and the treatment of patients is disclosed. The treatment and detection involve the use of families of chlorins, families of purpurins and families of metal complexes of chlorins and purpurins. The purpurins and their metal complexes have the structures of FIGS. 1 , 7, 14-18, 29-38, 44-48 and 54-58 of the attached drawings. The chlorins and their metal complexes have the formulas of FIGS. 2 , 8, 19, 20, 22, 23, 24, 25, 27, 28, 39, 40, 42, 43 and 49-53 of the attached drawings. Solutions of the purpurins, of the foregoing and other chlorins and of the metal complexes which are physiologically acceptable for intravenous administration are also disclosed, as are emulsions or suspensions of the solutions. The solvent for the solutions can be a product of the reaction of ethylene oxide with castor oil.

Abstract: The invention relates to coryneform microorganisms capable of assimilating lactose which carry a recombinant DNA capable of conferring the ability to assimilate lactose on coryneform microorganisms; and to a process for producing L-amino acids which comprises culturing said coryneform microorganism capable of assimilating lactose in a culture medium containing lactose to form an amino acid, and recovering said amino acid accumulated in the culture broth. Further, the invention relates to a method for preparing recombinant plasmids containing a DNA fragment essential to the expression of a gene in coryneform microorganisms.

Abstract: Trans-4-hydroxy-L-proline is produced microbially, especially by the cultivation of a microorganism of the genus Clonostachys, Gliocladium or Nectria.

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with a D-configuration hydroxyproline ether or thioether converts bradykinin agonists into bradykinin antagonists. The invention further includes the intermediate compounds and additional modifications at other positions within the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract: Disclosed are a process for producing 4-hydroxy-L-proline by the conversion of 4-hydroxy-2-oxoglutaric acid in an aqueous medium in the presence of an amino group donor and an enzyme source belonging to the genus Escherichia and capable of converting 4-hydroxy-2-oxoglutaric acid into 4-hydroxy-L-proline; and a microorganism which belongs to the genus Escherichia, holds a recombinant DNA incorporating a gene coding for .gamma.-glutamylkinase released from the feedback inhibition caused by L-proline, and contains the above enzyme source.

Abstract: The present invention provides a process for producing trans-L-hydroxyproline, which comprises culturing a microorganism which is capable of decomposing amino acids other than trans-L-hydroxyproline but which is substantially incapable of decomposing trans-L-hydroxyproline in a culture medium containing collagen hydrolyzate, and recovering trans-L-hydroxyproline from the resulting culture.The process enhances the content of trans-L-hydroxyproline based on the total weight of amino acids contained in collagen hydrolyzate, and enables efficient production of trans-L-hydroxyproline which is useful as a starting material for the synthesis of medicines.

Abstract: Culturing an L-amino acid producing microorganism belonging to the genus Brevibacterium or corynebacterium and having a resistance to a dipeptide containing glutamic acid or aspartic acid gives L-amino acids in high yield.

Abstract: A microbiologically produced, thermostable N-acylproline-acylase and a process for obtaining it from Comamonas testosteroni DSM 5416 and Alcaligenes denitrificans DSM 5417. The enzyme is useful for the synthesis of L-proline from various N-acyl-L-proline derivatives.

Abstract: Families of chlorins, families of purpurins and metal complexes thereof are disclosed. The purpurins and their metal complexes have the structures of FIGS. 1, 7, 14-18, 29-38, 44-48 and 54-58 of the attached drawings. The chlorins and their metal complexes have the formulas of FIGS. 2, 8, 19, 20, 22, 23, 24, 25, 27, 28, 39, 40, 42, 43 and 49-53 of the attached drawings. Solutions of the purpurins, of the foregoing and other chlorins and of the metal complexes which are physiologically acceptable for intravenous administration are also disclosed, as are emulsions or suspensions of the solutions. The solvent for the solutions can be a product of the reaction of ethylene oxide with castor oil. A method for detecting and treating tumors in human and animal patients is also disclosed. The method comprises administering one of the purpurins, chlorins or metal complexes to the patient.

Abstract: An enzymatic process for the enantiomer-specific preparation of mercapto alkanoic acids by stereoselective hydrolysis of mercapto or thioester alkanoic acid esters.

Abstract: Monoclonal antibodies are disclosed that may be produced by hybridomas obtained by fusing a mouse spleen cell immunized with an ADRIAMYCIN.RTM.-resistant human tumor cell and a mouse myeloma cell and which inhibit selectively the growth of cancer cells possessing pleiotropic drug resistance or enhance their sensitivity to said drug.

Abstract: Process is described for the production of L-amino acids of general formula I ##STR1## in which R.sub.1 means an alkyl radical with at most 12 carbon atoms optionally substituted by hydroxy groups, mercapto groups, halogen atoms, amino groups, carbonyl groups or guanidino groups and/or interrupted by oxygen atoms, nitrogen atoms or sulfur atoms, and in the case of mercapto compounds of formula I also their dithio compounds, characterized in that the microorganism Nocardia spec. DSM 3306 or its enzymes are allowed to act on a D,L-imidazolidinedione derivative of general formula II ##STR2## in which R.sub.1 has the above-named meaning or, in the case of mercapto compounds of formula II, also in their dithio compounds.

Abstract: Families of chlorins, families of purpurins and metal complexes thereof are disclosed. The purpurins and their metal complexes have the structures of FIGS. 1, 7, 14-18, 29-38, 44-48 and 54-58 of the attached drawings. The chlorins and their metal complexes have the formulas of FIGS. 2, 8, 19, 20, 22, 23, 24, 25, 27, 28, 39, 40, 42, 43 and 49-53 of the attached drawings. Solutions of the purpurins, of the foregoing and other chlorins and of the metal complexes which are physiologically acceptable for intravenous administration are also disclosed, as are emulsions or suspensions of the solutions. The solvent for the solutions can be a product of the reaction of ethylene oxide with castor oil. A method for detecting and treating tumors in human and animal patients is also disclosed. The method comprises administering one of the purpurins, chlorins or metal complexes to the patient.

Abstract: A process for recovering a high-purity L-amino acid from a fermentation liquor obtained by fermentation or an enzymic method, which comprises removing the impurities contained in said fermentation liquor by passing said fermentation liquor through an ultrafilter membrane and then through an ion-exchange or adsorbent resin; concentrating or cooling the effluent thus obtained to result in crystallization of said L-amino acid, and isolating said crystalline L-amino acid from said fermentation liquor.

Abstract: A process for recovering a high-purity L-amino acid from a fermentation liquor obtained by fermentation or an enzymic method, which comprises removing the impurities contained in said fermentation liquor by passing said fermentation liquor through an ultrafilter membrane and then through an ion-exchange or adsorbent resin; concentrating or cooling the effluent thus obtained to result in crystallization of said L-amino acid, and isolation said crystalline L-amino acid from said fermentation liquor.

Abstract: A substantial elevation of the space-time yield is achieved in the preparation of D-.alpha.-amino acids by means of the biotransformation of hydantoins which are monosubstituted in the 5-position in an aqueous medium in the presence of cells of the microorganism Agrobacterium radiobacter if the biotransformation is carried out under a elevated pressure at the start of the reaction. A further improvement results if this elevated pressure is maintained for a period of at least 16 hours, then removed and the biotransformation continued at atmospheric pressure.

Abstract: Disclosed is a process for producing histidine by transforming a host microorganism belonging to the genus Corynebacterium or Brevibacterium with a recombinant DNA of a DNA fragment containing a gene involved in the biosynthesis of histidine and a vector DNA, culturing the transformant in a nutrient medium, accumulating histidine in the culture medium and recovering histidine therefrom.

Abstract: Novel DNA sequences which code for the production of Pichia histidinol dehydrogenase, phosphoribosyl-ATP-cyclohydrase and phosphoribosyl-ATP-pyrophosphohydratase are provided. Novel constructs including these sequences, as well as transformed organisms therewith are provided. A method for isolation of functional genes from yeast strains of the genus Pichia is also provided. In addition, process for the integrative transformation of yeast strains of the genus Pichia is provided.

Abstract: A biocatalytic method for producing a desired amino acid is disclosed. The method involves contacting a 2-ketoacid corresponding to the desired amino acid with lactic acid, aspartic acid and ammonia, or salts thereof, in the presence of:(a) one or more transaminase enzymes capable of catalyzing the conversion of the 2-ketoacid and L-aspartic acid to the desired amino acid and oxaloacetic acid;(b) a malate-lactate transhydrogenase enzyme capable of catalyzing the conversion of lactic acid and oxaloacetic acid to pyruvic acid and malic acid;(c) a fumarase enzyme capable of catalyzing the conversion of malic acid to fumaric acid; and(d) an aspartate-ammonia lyase enzyme capable of catalyzing the conversion of fumaric acid and ammonia to aspartic acid.

Abstract: L-Glutamic acid is produced in a high yield by cultivating an L-glutamic acid-producing microorganism which requires oleic acid but does not require biotin for growth in a culture medium containing an oleic acid compound and a biotin compound of no less than 100 .mu.g/liter as biotin, with carbohydrate and acetic acid as carbon sources being maintained in a weight ratio of about 80:20 through about 40:60.

Abstract: L-histidine is produced by culturing, in a nutrient medium, an L-histidine producing mutant microorganism belonging to the genus Corynebacterium. The mutant is resistant to a precursor for ubiquinone biosynthesis. L-histidine is accumulated in the culture liquor and is recovered therefrom.

Abstract: Non-conjugative episomes characterized by having a mutated proBA region are provided for conferring osmotic tolerance on osmotically sensitive hosts. The mutated DNA sequence overproduces at least one enzyme in the biosynthetic pathway for an amino acid which imparts the desired osmotic tolerance.Cell lines E. coli CSH26 were deposited at the A.T.C.C. on Sept. 20, 1982 and given accession number 39202.

Abstract: L-Histidine producing microorganisms which have been constructed by introducing a recombinant plasmid DNA inserted on a chromosomal DNA fragment into a recipient strain of the genus Bacillus. These microorganisms are employed to produce L-histidine in higher than normal yields. The recombinant plasmid DNA inserted is obtained from a donor mutant strain of Bacillus subtilis which is resistant to certain L-histidine antagonists. The resistant plasmid confers the properties of the mutant strain upon the recipient Bacillus subtilis to make its high yield of product even higher.

Abstract: L-histidine is produced by culturing, in a nutrient medium, an L-histidine producing mutant microorganism belonging to the genus Corynebacterium or Brevibacterium. The mutant is resistant to growth inhibition by an RNA polymerase inhibitor or requires adenine. L-histidine is accumulated in the culture liquor and is recovered therefrom.

Abstract: A method for the fermentative production of L-proline which comprises cultivating a L-proline-producing mutant of a microorganism belonging to the genus Serratia in a broth to produce and accumulate L-proline therein and collecting accumulated L-proline. The mutant is preferably that of Serratia marcescens which is deficient in L-proline oxidase and is resistant to proline analong under a high osmotic pressure.

Abstract: A process for producing L-proline by fermentation, comprising culturing a microorganism belonging to the genus selected from Corynebacterium, Arthrobacter, Brevibacterium, Microbacterium and Saccharomyces and capable of producing L-proline in a culture medium to accumulate L-proline in the cultured liquor and recovering L-proline therefrom, which process is characterized by the use of a culture medium containing at least one member selected from L-glutamic acid and D-, L- and DL-pyrrolidonecarboxylic acid in association with a carbon source, nitrogen source and inorganic compounds.

Abstract: A process for producing L-proline in the absence of light by cultivating Chlorella sp. 580 algae in an aqueous growth medium containing a high concentration of sodium chloride of up to 1M in the final stage of cultivation and providing an adequate supply of carbon in the form of acetate ion, until algae of high L-proline content are obtained, harvesting the algae and thereafter recovering L-proline from the algae.

Abstract: A microorganism of the genus Escherichia incorporated with a hybrid plasmid, which have been inserted with a DNA fragment possessing genetic information related to L-histidine production and obtained from a mutant of the genus Escherichia, resistant to a histidine-analogue, produces L-histidine in a high yield.

Abstract: A process for producing L-proline by cultivating Chlorella sp. 580 algae under high-intensity illumination in an aqueous growth medium containing a high concentration of sodium chloride (at least 1 M in the final stage of cultivation), providing an adequate supply of carbon, in a depth not exceeding approximately 20 cm of the aqueous medium, until algae of high L-proline content are obtained, harvesting the algae and thereafter recovering L-proline from the algae.

Abstract: A process for recovering L-proline from Chlorella sp. 580 algae without disrupting the L-proline synthesizing capability of the algae thereby permitting reuse of the proline depleted cells to produce additional amounts of L-proline. The process comprises cultivating Chlorella sp. 580 algae under high-intensity illumination in an aqueous growth medium containing a high concentration of sodium chloride (at least 1 M in the final stage of cultivation), providing an adequate supply of carbon, in a depth not exceeding approximately 20 cm of the aqueous medium, until algae of high L-proline content are obtained, harvesting the algae and thereafter diluting the harvested algae with water to a concentration below at least 0.

Abstract: A method for producing L-proline by fermentation which comprises culturing an L-proline producing mutant in a culture medium until L-proline is accumulated in the culture medium, and recovering the accumulated L-proline; said mutant belonging to the genus Brevibacterium, Corynebacterium or Microbacterium and being resistant to DL-3,4-dehydroproline.

Abstract: D-.alpha.-amino acids are produced by contacting a 5-substituted hydantoin with an effective amount of an enzyme capable of converting the 5-substituted hydantoin to the D-.alpha.-amino acid produced by a microorganism in an aqueous medium at a pH in the range of 4 to 9, the microorganism being capable of utilizing the D-isomer of the 5-substituted hydantoin as the sole nitrogen source, but substantially incapable of utilizing the L-isomer of the 5-substituted hydantoin as the nitrogen source and the substituent of the 5-position being such that upon reaction with the enzyme, an optically active D-.alpha.-amino acid isomer is produced; and recovering the D-.alpha.-amino acid which accumulates in the aqueous medium.