Abstract: The present invention relates to an isolated genetic sequence encoding a nonribosomal peptide synthetase (NRPS) protein which directs the biosynthesis of the antibiotic ramoplanin in microorganisms such as Actinoplanes sp. The isolated gene sequence serves as a substrate for bioengineering of antibiotic structures.

Abstract: Mutants of Kunitz domain 1 (ITI-D1) of human inter-?-trypsin inhibitor (ITI), are useful as inhibitors of human neutrophil elastase. Mutants characterized by one or more of the following substitutions (numbered to correspond to bovine pancreatic trypsin inhibitor, the archetypal Kunitz domain) are of particular interest: (a) Val15 or Ile15, (b) Ala16, (c) Phe18, (d) Pro19, (e) Arg1, (f) Pro2, and/or (g) Phe4.

Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X[Formula I] wherein X is a linker group having 2–5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.

Abstract: Recombinant host cells of the suborder Cystobacterineae, genus Stizmatella, containing recombinant expression vectors that encode heterologous epothilone polyketide synthase (PKS) genes and can produce epothilones at high levels are provided.

Abstract: Polynucleotides, such as DNA, are provided which accelerate the biosynthesis of a HMG-CoA reductase inhibitor, ML-236B, in an ML-236B producing micro-organism when introduced in the ML-236B producing micro-organism. Pravastatin, which is an HM-CoA reductase inhibitor, can be obtained using Streptomyces carbophilus by microbial conversion of ML-236B produced by Pencillium citrinum. The polynucleotides encode a gene (such as micA (polyketide synthase), mlcB (polyketide synthase), micE (efflux pump) or mlcR (transcription factor). Provided are vectors into which such polynucleotides are incorporated; host cells transformed by such vectors; and proteins expressed by such vectors. A method for producing ML-236B using such polynucleotides and/or proteins which comprises recovering ML-236B from a culture of the host cell.

Abstract: A process for the production of an L-amino acid wherein coryneform bacteria (e.g. Coryneform glutamicum) in which expression of the mqo gene coding for malate quinone oxidoreductase is attenuated are fermented to produce a desired amino acid, and the amino acid is concentrated in the medium or cells and isolated. Optionally, further genes in the biosynthetic pathway of the desired amino acid are enhanced, and/or metabolic pathways that reduce formation of the amino acid are suppressed.

Abstract: The invention relates to an isolated polynucleotide having a polynucleotide sequence which codes for the sigC gene from Corynebacterium glutamicum, and a host-vector system having a coryneform host bacterium, such as Corynebacterium glutamicum, and a vector which carries at least the sigC gene according to SEQ ID No 1, and the use of polynucleotides which comprise the sequences according to the invention as hybridization probes.

Abstract: The present invention relates to a penicillin binding protein, DNA encoding the protein and methods of producing L-glutamic acid in Corynebacterium glutamicum, which has a reduction of penicillin binding protein activity.

Abstract: The present invention relates to polynucleotide molecules comprising sequences encoding avec gene products, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of Streptomyces avermitilis. AveC genes, homologs and partial homologs thereof are described for S. avermitilis, S. hygroscopicus, and S. griseochromogenes, respectively. The present invention further relates to vectors, host cells, and mutant strains of Streptomyces 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: The present invention relates to protease subtilase enzyme, characterized by an insertion in at least one active site loop. The enzymes exhibit improved wash performance in a detergent in comparison to its parent enzyme if it is a subtilase variant.

Abstract: Novel fetal genes (fls353 and fls485) have been successfully isolated from human fetal liver-derived cDNAs. These genes were specifically expressed in tissues including fetal tissues which are thought to contain a large number of undifferentiated cells and actively differentiating/proliferating cells. High levels of expression of these genes were observed also in a variety of cancer cells. The proteins and genes encoding the proteins can be used as the tool for developing drugs for the treatment of tumors.

Abstract: A subject of the invention, in all possible isomer forms as well as their mixtures, is the compounds of formula (I): in which either R1: H or CH3 and R2: cyclohexyl substituted by an amine, a (CH2)b-C?N radical or R1 and R2 together with the nitrogen which carries them form a ring with 3, 4 or 5 carbons optionally substituted by an amine R3: hydrogen, methyl or hydroxyl R4: hydrogen or hydroxyl R: represents a linear, branched or cyclic chain T: hydrogen, methyl, CH2CONH2, CH2C?N, a (CH2)2NH2 or (CH2)2Nalk+X? radical, X halogen and alk alkyl Y: hydrogen, hydroxyl, halogen or OSO3H, W: H or OH, Z: H, CH3. The compounds of formula (I) have antifungal properties.

Abstract: Spinosyn biosynthetic genes from Saccharopolyspora spinosa, spinosyn producing microorganisms transformed with the biosynthetic genes, methods using the biosynthetic genes to increase production of spinosyn insecticidal macrolides, and methods using the genes or fragments thereof to change the products produced by spinosyn-producing microorganisms are provided.

Abstract: Recombinant E. coli host cells that comprise recombinant DNA expression vectors that drive expression of methylmalonyl CoA mutase from Propionibacterium shermanii or Streptomyces cinnamonensis as well as Propionibacterium shermanii epimerase can produce S-methylmalonyl CoA, a required substrate for the production of polyketides by most modular polyketide synthases and is not present in wild-type E. coli host cells.

Abstract: Linking sequences which modulate cross-talk between modules of Type I polyketide synthases have been identified. Thus, arbitrarily chosen modules can be mixed and matched by supplying the appropriate linkers to obtain desired polyketide synthases and new polyketides. The modules are provided suitable linkers so that the polyketide chain is passed from one module to the other in the correct sequence. Synthetic peptides which mimic linkers can be used to inhibit the synthesis of polyketides. Kinetic channeling, both intrapolypeptide and interpolypeptide, of diketide intermediates in a Type I polyketide synthase can occur.

Abstract: Methods are provided for purification of epothilone D and epothilone D analogs from epothilone producing cells such as, for example, Sorangium cellulosum and Myxococcus xanthus (recombinant). Epothilone can be purified from fermentation broth, for example by using resins, chromatography, and crystallization. Epothilone D can be crystallized from a binary solvent system in which water is the forcing solvent.

Abstract: The invention relates to an isolated polynucleotide from Corynebacterium glutamicum having a polynucleotide sequence which encodes the sigma factor M (sigM) gene, and a host-vector system having a coryneform host bacterium in which the sigM gene is present in enhanced form and a vector which carries at least the sigM gene according to SEQ ID No 1, and the use of polynucleotides which comprise the sequences according to the invention as hybridization probes.

Abstract: The invention provides DNA, heterologous host cells capable of transcribing, translating or expressing said DNA and methods employing such host cells and cultures thereof for an improved in vivo production of acylated cephalosporins with higher yield. According to the invention, a host cell is provided comprising an enzyme having expandase activity which is predominantly localized in the cytosol (as opposed to localized mainly in or with the peroxisomes or microbodies) of the host cell.

Abstract: Compositions and methods are provided for the enhanced in vitro synthesis of polypeptides. In order to improve the performance of in vitro protein synthesis reactions, metabolic inhibitors, or manipulation of a source organism, is used to diminish or avoid the action of enzymes responsible for undesirable amino acids production or depletion. A homeostatic system may be used for production of ATP, where the required high energy phosphate bonds are generated in situ, e.g. through coupling with an oxidation reaction. The homeostatic energy source will typically lack high energy phosphate bonds itself, and will therefore utilize free phosphate in the reaction mix during generation of ATP. The homeostatic energy source is provided in combination with an enzyme that catalyzes the creation of high energy phosphate bonds and with an enzyme that can use that high energy phosphate bond to regenerate ATP.

Abstract: The invention provides methionyl tRNA synthetase (tRS) enzymes from Staphylococcus aureus and methods of producing such tRS by recombinant techniques. Also provided are methods for utilizing tRS for the protection against infection, particularly bacterial infection, most particularly Staphylococcus aureus infection.