Abstract: A transformed yeast is disclosed, comprising at least one gene encoding neutral trehalase or trehalose-6-phosphate synthase which gene has been modified such that it differs from a corresponding wild-type gene encoding neutral trehalase or trehalose-6-phosphate synthase, the yeast having as a result a different trehalose content from the untransformed parent yeast. The sugar resistance and drying resistance of the yeast compared to those of the untransformed strain are thereby improved.
Type:
Grant
Filed:
March 22, 1991
Date of Patent:
May 17, 1994
Assignee:
Gist Brocades, N.V.
Inventors:
Marianne Driessen, Klaas A. Osinga, Margareta A. Herweijer
Abstract: A method for selecting amino acid residues is disclosed which upon replacement will give rise to an enzyme with an altered substrate specificity. New mutant glucose isomerases with an altered substrate specificity are provided according to this method. These altered properties are useful in starch degradation and in other sugar conversion reactions.
Type:
Grant
Filed:
January 4, 1991
Date of Patent:
May 10, 1994
Assignee:
Gist-brocades, N.V.
Inventors:
Anne-Marie Lambeir, Ignace Lasters, Wilhemus J. Quax, Jan M. Van der Laan
Abstract: Methods are provided for improved production of hIL-3 either in glycosylated form from mammalian and yeast cells or in unglycosylated form from prokaryotes. Recombinantly produced human IL-3 is purified in a series of steps, initially employing hydrophobic interaction, followed by ion exchange chromatography and gel filtration.
Type:
Grant
Filed:
March 13, 1990
Date of Patent:
April 19, 1994
Assignee:
Gist-brocades N.V.
Inventors:
Lambertus C. J. Dorssers, Gerard Wagemaker, Yvonne J. Vos, Robert W. Van Leen, Maria L. N. Persoon
Abstract: 9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86. Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.-trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield. The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids.
Abstract: The oxidative deterioration of water-containing products for human consumption, e.g. beverages and oil and/or fat based products is minimized by introduction of immobilized yeast. Yeast is immobilized in and/or on a solid material which allows only very slow penetration by water. Thin layers material of such a yeast-bearing solid, e.g. paraffin, wax, can be applied to the lining of crown corks. The yeast will retain sufficient viability, even after pasteurization of the contents of a container closed with the crown cork. The yeast will minimize the oxygen concentration in the contents between the time of pasteurization and eventual consumption of the contents.
Type:
Grant
Filed:
December 13, 1991
Date of Patent:
March 29, 1994
Assignee:
Gist-Brocades, N.V.
Inventors:
Luppo Edens, Farrokh Farin, Antonius F. Ligtvoet, Johannes B. Van Der Plaat
Abstract: The invention pertains to a method for the production of a biologically active modified protein derived from a starting protein having essentially the same kind of biological activity with an attendant modulation effect on, particularly increase of, the stability as compared with that of the starting protein. The method comprises substituting an arginine residue for a lysine residue of the starting protein at a site that can sterically accommodate the substitution, without substantially altering the biological activity of the starting protein, said site being preferably of low solvent accessibility, at interfaces between domains or sub-units of the starting protein.
Type:
Grant
Filed:
August 25, 1989
Date of Patent:
March 1, 1994
Assignees:
Plant Genetic Systems, Gist-brocades
Inventors:
Nadir Mrabet, Ignace Lasters, Patrick Stanssens, Gaston Matthyssens, Shoshana Wodak, Wilhelmus J. Quax
Abstract: Novel microbial host strains are provided which are transformed by a vector molecule comprising a DNA fragment encoding a lipolytic enzyme and a marker for selection, capable of producing active lipase. Said DNA fragment is preferably derived from a Pseudomonas species.
Type:
Grant
Filed:
September 25, 1989
Date of Patent:
January 11, 1994
Assignee:
Gist-brocades NV
Inventors:
Peter M. Andreoli, Maria M. J. Cox, Farrokh Farin
Abstract: A process for the preparation of at least one compound of a formula selected from the group consisting of ##STR1## and their salts and esters wherein X is selected from the group consisting of hydrogen and a substituent such as halogen and acetoxy comprising diazotizing a compound of the formula ##STR2## and salts and esters thereof wherein X has the above definition and brominating the resulting diazotized compound with at least an equimolar amount of a nitrosating agent in the presence of 1 to 5 equivalents of a strong acid in solution or suspension in a mixture of water and an at least partially water-miscible organic solvent with the amount of water being 1 to 20% by volume containing at least equimolar amounts of hydrogen bromide and bromine which bromo compounds are useful intermediates for the preparation of penicillanic acid-1,1-dioxide and its derivatives and novel 6-diazo-intermediates.
Type:
Grant
Filed:
May 8, 1992
Date of Patent:
November 30, 1993
Assignee:
Gist-Brocades N.V.
Inventors:
Peter W. Henniger, Johannes K. van der Drift
Abstract: Oral pharmaceutical compositions in unit dosage form, especially capsules, comprising solid Colloidal Bismuth Subcitrate (CBS), optionally one or more auxilliary medicaments and excipients, the dosage units having a packing density of between 0.06 and 0.60 grams of CBS per ml.
Abstract: A biological denitrification is provided in which ammonium ion is used as an electron donor in the denitrification. The process may advantageously be used under conditions of high ammonium ion concentrations in waste water or to remove ammonium ion from manure, soil or surface water. Microorganisms are described which may be used in these processes.
Abstract: The subject invention describes the cloning and overexpression of leader peptidase genes. A method for isolating a leader peptidase gene is disclosed. Overexpression of the signal peptidase in a suitable host species leads to an enhanced rate of protein processing.
Type:
Grant
Filed:
February 28, 1991
Date of Patent:
September 21, 1993
Assignee:
Gist-brocades, N.V.
Inventors:
Jan M. Van Dijl, Hilde E. Smith, Sierd Bron, Wilhelmus J. Quax, Gerard Venema
Abstract: Carboxyl esterase is inactivated by several chemical compounds such as naproxen or diclofop. By substituting or modifying certain basic residues of the carboxyl esterase, this enzyme shows improved stability properties during application. In this way it is possible to perform stereospecific hydrolysis reactions on industrial scale even at high substrate concentrations.
Type:
Grant
Filed:
May 14, 1992
Date of Patent:
August 24, 1993
Assignee:
Gist-brocades
Inventors:
Johanna H. G. M. Mutsaers, Cornelis J. van der Laken, Cornelis P. Broekhuizen, Wilhemus J. Quax
Abstract: Novel methods and novel industrial unicellular microorganism strains, particularly industrial Bacillus strains, are provided for enhanced production of endogenous and exogenous polypeptides. Cloning vehicles containing the gene expressing the polypeptide of interest are introduced into a compatible host. Transformed hosts harboring the introduced vehicle in a stable way by integration of the vehicle into the host cells chromosome are selected Efficient transfer of the vehicle containing the gene of interest is achieved, with the resulting industrial strain transformants being effective, stable producers of the desired polypeptide product.
Type:
Grant
Filed:
May 13, 1991
Date of Patent:
August 24, 1993
Assignee:
Gist-brocades, NV
Inventors:
Johan P. M. Sanders, Johannes A. Van Den Berg, Peter M. Andreoli, Yvonne J. Vos, Jan H. Van EE, Leo J. S. M. Mulleners
Abstract: A substance is prepared having interleukin-8 inhibiting activity by extracting psoriatic scales and separating the extract on several successive HPLC columns, using an assay for IL-8i activity based on the inhibition of myeloperoxidase release and/or of the neutrophil chemotaxis of a reference sample.The substance is suitable for the preparation of anti-inflammatory medicines.
Abstract: Novel methods and novel industrial Bacillus strains are provided for enhanced production of serine protease. Plasmid constructs comprising the serine protease gene are introduced into a compatible host, generally a Bacillus already overproducing serine protease. Preferred host cells are those from Bacillus novo sp. PB92 and the preferred serine protease gene also originates from Bacillus PB92. Integration and maintenance of the plasmid in the host cell chromosome can be achieved by including a temperature sensitive origin of replication in the plasmid construct and growing under selective conditions.
Type:
Grant
Filed:
February 29, 1988
Date of Patent:
June 8, 1993
Assignee:
Gist-Brocades, NV
Inventors:
Christiaan A. G. van Eekelen, Johannes C. van der Laan, Leo J. S. M. Mulleners
Abstract: DNA constructs that are useful for providing secretory expression of heterologous polypeptides in yeast comprising a DNA sequence that includes a Kluyveromyces .alpha.-factor leader sequence linked to the heterologous polypeptide by a yeast processing signal. Constructs employing the K. lactis .alpha.-factor leader and processing signal sequences, with and without spacer, linked to prochymosin are exemplified.
Type:
Grant
Filed:
April 9, 1990
Date of Patent:
June 8, 1993
Assignees:
Chiron Corporation, Gist-Brocades
Inventors:
Anthony J. Brake, Johan A. Van Den Berg
Abstract: Novel vectors are provided for identifying secretory signal sequences from DNA fragments of unicellular microorganisms. The plasmids comprise a multiple cloning site with restriction sites in reading frame with a structural gene which permits rapid screening of the secreted expression product. Optionally, the vectors may include a promoter region upstream from the multiple cloning site. The invention is exemplified with Bacillus. Specific secretory signal sequences have been isolated with those vectors, allowing for efficient secretion into the supernatant, and not just to the periplasmic space to provide proteins in economically high yields. Secretory sequences are provided superior to other previously known sequences.
Type:
Grant
Filed:
December 13, 1990
Date of Patent:
May 18, 1993
Assignee:
Gist-brocades
Inventors:
Hilde E. Smith, Jan H. Van Ee, Ben P. H. Peeters, Sierd Bron, Gerard Venema
Abstract: A multi-purpose pharmaceutical tablet which can either be readily swallowed or dissolved in water to give a dispersion, comprising a tetracycline, microcrystalline cellulose or microfine cellulose, low substituted hydroxypropylcellulose and a thickening agent, preferably hydroxypropyl methylcellulose, and optionally other conventional adjuvants. The tablet may be easily swallowed as such, and when immersed in water, it affords a very fine dispersion within 30-60 seconds. The tablet may be prepared by direct compression, or by a wet granulation process in which a granulate is used which contains tetracycline and any substantial amount of a wet binding substance.
Type:
Grant
Filed:
April 29, 1992
Date of Patent:
May 18, 1993
Assignee:
Gist-Brocades, N.V.
Inventors:
Piet J. Akkerboom, Robert De Cocq, Maria Wegman
Abstract: The invention provides a process for the preparation of 2,6-difluorobenzamide which comprises subjecting 2,6-difluorobenzonitrile to the action of a suitable hydrolysing microorganism or nitrilase extract therefrom; and Rhodococcus Sp. NCIB 12218 or a mutant thereof, suitable for use in the process.
Type:
Grant
Filed:
August 21, 1990
Date of Patent:
April 27, 1993
Assignees:
Gist-Brocades N.V., Shell Internationale Research Maatschappij B.V.
Inventors:
Kenneth H. Clifford, Philip J. Geary, Robert J. Pryce
Abstract: Novel vectors are disclosed for use in filamentous fungi such as Aspergillus sp. in particular, whereby protein coding regions may be inserted therein to achieve expression or expression followed by secretion of the coded protein from the host. Signal peptide sequences and promoter sequences valuable for this purpose are disclosed as are expression vectors containing coding regions native or foreign to the fungal host. In accordance with the invention, a filamentous fungus such as Aspergillus may be provided with foreign or natural coding regions associated with foreign or natural promoter sequences and optionally signal peptide sequences which can be used to control the expression and/or secretion of the proteins encoded by these coding regions.
Type:
Grant
Filed:
December 20, 1985
Date of Patent:
March 30, 1993
Assignee:
Gist-Brocades N.V.
Inventors:
David I. Gwynne, Francis P. Buxton, Mark H. Pickett, Roger W. Davies, Claudio Scazzocchio