Abstract: The present invention is directed to long-lasting therapeutic formulations and their methods of use wherein the formulation comprises a genetically modified micro-organ that comprises a vector which comprises a nucleic acid sequence operably linked to one or more regulatory sequences, wherein the nucleic acid sequence encodes a therapeutic polypeptide, such as erythropoietin or interferon alpha.

Abstract: Aureolic acid derivatives, process for obtaining them and uses thereof. This invention provides a bacterial strain that produces compound belonging to the family of aureolic acids useful in the treatment of cancer or nervous system diseases.

Abstract: Oviedomycin derivatives, method for obtaining same and use thereof. This invention relates to oviedomycin derivatives obtained by fermentation of recombinant bacterial strains. The invention also relates to the methods used to obtain the recombinant strains and to produce the oviedomycin derivatives. The invention further relates to bacterial strains that can be used to produce oviedomycin derivatives. Finally, said oviedomycin derivatives are applicable in the field of the human health, specifically to produce drugs for the treatment of tumour diseases.

Abstract: Glycosylated indolocarbazoles, method for obtaining same and uses thereof. This invention relates to rebeccamycin and staurosporine derivatives obtained by fermentation of recombinant bacterial strains. The invention also relates to the methods used to obtain the recombinant strains and the production of rebeccamycin and staurosporine derivatives. The invention also relates to bacterial strains that are of use for the production of rebeccamycin and staurosporine derivatives. Lastly, the rebeccamycin and staurosporine derivatives described herein are applicable to the field of human health, specifically for manufacturing drugs that are of use in the treatment of tumour, neurological and inflammatory diseases.

Abstract: Nucleotide and protein sequences that encode enzymes that change carbon flux through metabolic pathways that lead to lactic acid or fumarate production in a host cell, such as a R. oryzae cell, are provided. Methods of manipulating carbon flux in a cell also are provided.

Abstract: The invention relates to isolated genes encoding Xenorhabdus toxin complex (TC) proteins, and transgenic plants and host cells expressing Xenorhabdus toxin complex (TC) proteins and having resistance to insects.

Abstract: The present invention provides compounds characterized by the formula (I), where each of the substituent radicals is described in the specification. The invention also describes the use of said compounds in the treatment of various diseases, including: cancer or tumoral processes in general, Paget's disease, hypercalcaemia, hypercalciuria and neurological diseases (inter alia, Parkinson's, Alzheimer's, Huntington's).

Abstract: The invention relates to a system for stable maintenance of a plasmid, to host cells for use in this system and to methods of using the system to obtain a plasmid useful in medical applications. In particular, the invention provides transformed host cell containing: i) a chromosomal gene which inhibits cell growth; and ii) a plasmid encoding an antisense sequence, wherein the antisense sequence encoded by the plasmid inhibits the action of the chromosomal gene, thereby permitting cell growth and a method for stable maintenance of a plasmid in a host cell in vivo.

Abstract: Nucleotide sequences and genetic constructs that can be used to regulate genes encoding enzymes that change carbon flux through metabolic pathways that lead to lactic acid or fumarate production in a host cell, such as a R. oryzae cell, are provided. Methods of manipulating carbon flux in a cell also are provided.

Abstract: The present invention provides novel plastid transit peptides that direct localization of attached moieties (e.g., polypeptides) into plant plastids. The present invention also relates to methods and compositions for localizing polypeptides to plant plastids including, but not limited to, transgenic plant production.

Abstract: The present invention is directed to methods and compositions for microbial based production of pravastatin. The compositions of the invention include novel strains of microorganisms that are capable of efficiently hydroxylating compactin (ML-236 B) resulting in production of pravastatin. In particular, the microorganisms of the invention are genetically engineered to express both cytochrome P-450 and the fdxshe or fdxshe-like protein. The invention further relates to the use of such microorganisms in processes designed for production of pravastatin for use in treatment of disease such as hypercholesterolemia and hyperlipidemia.

Abstract: The present invention relates to isolated promoter sequences, particularly a promoter isolated from Aspergillus niger designated herein as A4-L or A4 and DNA constructs and vectors including the same.

Abstract: Methods are provided for increasing and altering the timing of antibiotic production in Streptomyces species, particularly S. coelicolor and S. lividans, by functionally deleting the S. coelicolor scbA and scbR genes, respectively, or their homologues. Also provided are strains having such mutations, and methods of producing antibiotics using such strains. Also provided are methods for identifying strains in which functional deletion of the scbA and/or scbR genes or their homologues leads to the above effects.

Abstract: Novel polyketides and novel methods of efficiently producing both new and known polyketides, using recombinant technology, are disclosed. In particular, a novel host-vector system is described which is used to produce polyketide synthases which in turn catalyze the production of a variety of polyketides.

Abstract: Disclosed is a process for identifying clones having a specified activity of interest, which process comprises (i) generating one or more expression libraries derived from nucleic acid directly isolated from the environment; and (ii) screening said libraries utilizing a fluorescence activated cell sorter to identify said clones. More particularly, this is a process for identifying clones having a specified activity of interest by (i) generating one or more expression libraries derived from nucleic acid directly or indirectly isolated from the environment; (ii) exposing said libraries to a particular substrate or substrates of interest; and (iii) screening said exposed libraries utilizing a fluorescence activated cell sorter to identify clones which react with the substrate or substrates.

Abstract: A novel soybean cultivar, designated 0491739, is disclosed. The invention relates to the seeds of soybean cultivar 0491739, to the plants of soybean 0491739 and to methods for producing a soybean plant produced by crossing the cultivar 0491739 with itself or another soybean variety. The invention further relates to hybrid soybean seeds and plants produced by crossing the cultivar 0491739 with another soybean cultivar.

Abstract: A novel soybean cultivar, designated 13873, is disclosed. The invention relates to the seeds of soybean cultivar 13873, to the plants of soybean 13873 and to methods for producing a soybean plant produced by crossing the cultivar 13873 with itself or another soybean variety. The invention further relates to hybrid soybean seeds and plants produced by crossing the cultivar 13873 with another soybean cultivar.

Abstract: The invention relates to high-level production of pHBA in green plants using a unique expression cassette. The latter comprises a chorismate pyruvate lyase (CPL) coding sequence operably linked to a suitable promoter capable of driving protein expression in higher plants. Additionally, the CPL cassette comprises a sequence encoding a chloroplast transit peptide, its natural cleavage site, and a small portion of the transit peptide donor protein fused to the N-terminus of CPL. The chloroplast targeting sequence targets the foreign protein to the chloroplast compartment and aids in its uptake into the organelle. The cleavage site is unique to the transit peptide, and cleavage of the chimeric protein encoded by the cassette at this site releases a novel polypeptide that has full enzyme activity, comprising the mature CPL enzyme and a small portion of the transit peptide donor.

Abstract: Isolation, cloning and sequencing of the cluster of genes involved in the biosynthesis of the carbapenem thienamycin by streptomyces cattleya, and the use of those genes to increase thienamycin production, and/or related antibiotics, in the producing strains, and obtaining new derivatives by means of genetic manipulation which implies gene expression, mutagenesis by gene replacement and combinatorial biosynthesis.

Abstract: Provided herein are heretofore-unknown strains of Streptomyces that are unable to express undecylprodrodigiosin, actinorhodin, or both, as well as novel vectors that permit the creation of chromosomal mutations in Streptomyces and do not insert selection markers in the genome of Streptomyces, along with vectors and methods for transferring large segments of DNA into the Streptomyces and Psuedomonas chromosome by conjugation.

Abstract: The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding an aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of S. avermitilis. The present invention further relates to vectors, host cells, and mutant strains of S. avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.

Abstract: A method for in vivo production of a library in cells comprising a multitude of mutated genetic elements, wherein an error-prone polymerase is used in each ancestral cell to replicate all or a part of a genetic element independently of the host chromosomal replication machinery. The genetic element comprises i) an origin of replication from which replication is initiated, ii) optionally a genetic marker, e.g. a gene conferring resistance towards an antibiotic, iii) a gene encoding the polypeptide of interest. Also methods for the generation of a DNA sequence encoding a desired variant of a polypeptide of interest, and for the determination of such a DNA sequence are described.

Abstract: The present invention provides a isolated bacteriophage useful as a tool for studying biological, biochemical, physiological and genetic properties of actinomycetes and other organisms which comprises a novel strain of Saccharomonospora having certain specified characteristics. The invention also relates to a process for the isolation of the said bacteriophage and/or DNA phage and to a novel universal growth medium which is particularly useful in the said process. Another embodiment of the process relates to a cloning vector which comprises a plasmid or bacteriophage comprising the phage DNA of the invention.

Abstract: Novel polyketides and novel methods of efficiently producing both new and known polyketides, using recombinant technology, are disclosed. In particular, a novel host-vector system is described which is used to produce polyketide synthases which in turn catalyze the production of a variety of polyketides.

Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds.

Abstract: This invention relates to an isolated nucleic acid fragment encoding a glycolysis or respiration protein. The invention also relates to the construction of a chimeric gene encoding all or a portion of the glycolysis or respiration protein, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the glycolysis or respiration protein in a transformed host cell.

Abstract: The present invention is directed to compositions and methods for producing avermectins, and is primarily in the field of animal health. The present invention relates to the identification and characterization of two novel genes, herein referred to as the aveR1 and aveR2 genes, that are involved in regulating avermectin polyketide synthase (PKS) expression and avermectin biosynthesis in Streptomyces avermitilis. The present invention is based on the discovery that inactivation of these genes results in an increase in the amount of avermectin produced by S. avermitilis.

Abstract: The invention concerns mutant microorganisms blocked in a step of Streptogramin biosynthesis and methods for preparing cells blocked in a step of Streptogramin biosynthesis.

Abstract: A positive selection vector is provided for the transformation and screening of Gram positive bacteria and particularly Bacillus sp. for the presence of foreign DNA. The vector comprises a mutant gene encoding a signal peptide processing mutation. Expression of the mutant gene in a Bacillus host cell which lacks the ability to metabolize sucrose is lethal when cells are grown in the presence of sucrose. Foreign DNA may be inserted into the vector so as to inactivate the mutant gene thereby permitting the cells to grow in the presence of sucrose and allowing for facile selection of transformants.

Abstract: Hybrid and novel polyketide synthases and polyketides are produced by use of a multiple vector system. The combinatorial possibilities offered by placing the various catalytic activities of PKS systems on separate vectors permits the construction of improved libraries of PKS and polyketides. In addition, polyketides can be produced in hosts that ordinarily do not produce polyketides by supplying, along with an expression system for the desired PKS, an expression system for holo ACP synthase.

Abstract: A cloning vector contains a DNA sequence derived from a Nocardioform microorganism, and is capable of expressing the DNA sequence in a host microorganism. Recombinant cholesterol oxidase is produced by a host microbial cell transformed with a cloning vector containing cholesterol oxidase encoding DNA derived from a Nocardioform microorganism. A method for determining cholesterol oxidase in a sample of fluid from a human includes contacting the sample with the Nocardioform microorganism derived recombinant cholesterol oxidase.

Abstract: A DNA molecule isolated from Streptomyces fradiae encodes the multi-functional proteins which direct the synthesis of the polyketide tylactone.