Abstract: A biologically pure isolate of a selected bacterium derived from Clostridium autoethanogenum is described which has improved efficiency in the production of ethanol by anaerobic fermentation of substrates comprising carbon monoxide. The bacterium can produce ethanol and acetate at an ethanol to acetate ratio of at least 1.0 and has a productivity of at least 1.2 g of ethanol/l of fermentation broth per day. The bacterium is also characterized in that it has substantially no ability to sporulate.

Abstract: The present invention relates to a process for the production of ethanol comprising both gasification and fermentation of feedstocks, and, in particular to a process for the production of ethanol comprising: a) passing a biomass feedstock to a first fermentation step wherein it is subjected to anaerobic fermentation at a pH below 6.0 and at a temperature in the range 20 to 700C to convert the biomass to a solution comprising acetic acid as the predominant product, b) passing a gasifiable feedstock to a gasification step wherein it is subjected to gasification to produce a gaseous mixture comprising carbon monoxide and hydrogen, and c) passing the solution comprising acetic acid from step (a) and the gaseous mixture from step (b) to one or more further fermentation steps wherein they are subject to fermentation to produce ethanol.

Abstract: Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane, docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sporulated bacteria.

Abstract: The invention relates to methods of capturing carbon by microbial fermentation of a gaseous substrate comprising CO. The methods of the invention include converting CO to one or more products including alcohols and/or acids and optionally capturing CO2 to improve overall carbon capture. In certain aspects, the invention relates to processes for producing alcohols, particularly ethanol, from industrial waste streams, particularly steel mill off-gas.

Abstract: The present invention relates to the construction, expression, and purification of synthetic or recombinant light chain (LC) botulinum neurotoxin genes from all botulinum neurotoxin serotypes. The methods of the invention can provide 1.1 g of the LC per liter of culture. The LC product is stable and proteolytically active. Methods of using the products of the invention are described.

Abstract: Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.

Abstract: Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria.

Abstract: Methods and compositions are provided for improving the production of products, such as fuel products like ethanol, in microorganisms. In particular, methods and compositions are described for improving ethanol production utilizing genes identified in Clostridium phytofermentans.

Abstract: The present invention describes a method for producing butanol by fermentation of carbohydrates using mixed populations of acidogenic-phase cells and solventogenic-phase cells of Clostridium in a solitary vessel. The present system as described does not require intermittent adjustment of pH or venting of headspace gases. The method provides a process for removal of the butanol product which does not irreversibly harm the cells and conditions are described where such cells may resume butanol synthesis in the same solitary vessel. The invention also describes compositions and biologically pure cultures which comprise the Clostridium cells as disclosed. Also, a biologically pure Clostridium beijerinkii strain NRRL No. B-50244 is disclosed.

Abstract: A method for monitoring cleaning of a surface includes applying an amount of transparent indicator material to an area of a surface and measuring the amount of transparent indicator material remaining on the surface. The transparent indicator material may be fixed on the surface by drying and, when a fluorescent material, may be measured through exposure to ultraviolet radiation.

Abstract: A method for monitoring cleaning of a surface includes applying an amount of transparent indicator material to an area of a surface and measuring the amount of transparent indicator material remaining on the surface. The transparent indicator material may be fixed on the surface by drying and, when a fluorescent material, may be measured through exposure to ultraviolet radiation.

Abstract: Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.

Abstract: Animal product free (APF) media and processes for the culture and fermentation of botulinum toxin producing Clostridium botulinum bacteria. The botulinum toxin obtained can be used for formulating and compounding botulinum toxin pharmaceutical compositions. The APF media can contain significantly reduced levels of meat or dairy by-products and use non-animal based products instead of the animal-derived products. Preferably, the APF media used are substantially free or free of animal derived products.

Abstract: Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.

Abstract: Botulinum neurotoxins, the most potent of all toxins, induce lethal neuromuscular paralysis by inhibiting exocytosis at the neuromuscular junction. The light chains (LC) of these dichain neurotoxins are a new class of zinc-endopeptidases that specifically cleave the synaptosomal proteins, SNAP-25, VAMP, or syntaxin at discrete sites. The present invention relates to the construction, expression, purification, and use of synthetic or recombinant botulinum neutoroxin genes. For example, a synthetic gene for the LC of the botulinum neurotoxin serotype A (BoNT/A) was constructed and overexpressed in Escherichia coli. The gene product was purified from inclusion bodies. The methods of the invention can provide 1.1 g of the LC per liter of culture. The LC product was stable in solution at 4° C. for at least 6 months. This rBoNT/A LC was proteolytically active, specifically cleaving the Glu-Arg bond in a 17-residue synthetic peptide of SNAP-25, the reported cleavage site of BoNT/A.

Abstract: In this application is described substrates for high-throughput assays of clostridial neurotoxin proteolytic activities. Two types of substrates are described for use in assays for the proteolytic activities of clostridial neurotoxins: (1) modified peptides or proteins that can serve as FRET substrates and (2) modified peptides or proteins that can serve as immobilized substrates. In both types a fluorescent molecules is present in the substrate, eliminating the requirement for the addition of a fluorigenic reagent. The assays described can be readily adapted for use in automated or robotic systems.

Abstract: The invention relates to certain stable vaccine compositions comprising a macrocyclic lactone compound, a milbemycin compound, an avermectin compound or mixtures thereof; at least one antigen; a dispersing agent; an adjuvant; a water soluble organic solvent; and saline or water or mixtures thereof. The invention further relates to stable compositions as described above of a macrocyclic lactone compound, a milbemycin compound, an avermectin compound or mixtures thereof, but without an antigen. The invention also relates to a method for preventing or controlling helminthiasis, infection by acarids and arthropod endo-and ectoparasites and bacterial and viral disease in warm-blooded animals by the parenteral administration of compositions of the invention. The invention further relates to a process for the preparation of the invention compositions.

Abstract: The present invention relates to the discovery that hop extract is useful as an antibacterial agent against the dangerous pathogens Clostridium botulinum, Clostridium difficile, and Helicobacter pylori at levels below that at which a flavor from the acids contained therein is objectionable. More specifically, a process and associated product is described herein, comprising applying a solution of hop extract to a food, beverage or other medium so that the final concentration of hop ingredients is about 1 ppm or higher in order to inhibit the growth of Clostridium botulinum, Clostridium difficile, and/or Helicobacter pylori.

Abstract: The present invention provides a system for the growth of C. tetani and production of Tetanus Toxin for use in formulating Tetanus Toxoid preparations. The system includes growth media that contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferred media are substantially free of animal-derived products.

Abstract: Disclosed are methods and devices for detection of bacteria based on recognition and infection of one or more selected strains of bacteria with bacteriophage genetically modified to cause production of an inducer molecule in the bacterium following phage infection. The inducer molecule is released from the infected bacterium and is detected by genetically modified bacterial bioreporter cells designed to emit bioluminescence upon stimulation by the inducer. Autoamplification of the bioluminescent signal permits detection of low levels of bacteria without sample enrichment. Also disclosed are methods of detection for select bacteria, and kits for detection of select bacteria based on the described technology.

Abstract: A hybrid botulinal neurotoxin is disclosed. In one embodiment, the neurotoxin comprises a combination of a botulinal neurotoxin heavy chain and light chain, wherein the light chain and heavy chain are not of the same serotype and wherein the heavy and light chains are linked by a homobifunctional sulfydryl linker. A method for creating hybrid neurotoxins comprised of different functional domains is also disclosed.

Abstract: Pharmaceutical applications of a chemodenervating agent reduce pain by altering release of pain and inflammation-mediating autocoids, with a duration of action between 12-24 weeks. The limiting factor in dosing for this application is weakness and paralysis created by higher doses of the chemodenervating pharmaceutical. This weakness and paralysis is mediated by action of the neurotoxin component of the chemodenervating pharmaceutical. The invention described herein represents a novel mechanism and pharmaceutical formulation which eliminates the neurotoxin component of the chemodenervating pharmaceutical, while retaining the cytotoxin component which provides an essential bioeffect for the relief of pain and inflammation. The invention allows for improvement in administering the pharmaceutical agent for the reduction of pain and/or inflammation without causing muscular weakness and paralysis.

Abstract: The present invention provides methods of validating the sterility of compositions which contain large quantities of lipids, and especially those lipid compounds which contain quantities of bacteriocidal agents such as antibiotics. The compositions may contain quantities of phospholipids in the form of liposomes, microcrystals, or microdroplets. The methods involve dissolving the lipid composition in a diluent solution, passing the solution through a filtration device, and then incubating microbes which may be captured by the filtration device to determine whether microorganisms are present in the composition.

Abstract: A process and composition for treating an animal waste in a waste holding facility to reduce sulfides and enhance efficient degradation of large amounts of organic matter with reduced odor. The process includes administering a probiotic material capable of promoting organic digestion to an animal and maintaining a sulfide gas concentration of less than 10 ppm from a waste produced by the animal. Maintaining a low sulfide gas concentration can be done by adding an innoculum of sulfide-utilizing bacteria to the waste produced by the animal.

Abstract: The present invention relates to the discovery that hop extract is useful as an antibacterial agent against the dangerous pathogens Clostridium botulinum, Clostridium difficile, and Helicobacter pylori at levels below that at which a flavor from the acids contained therein is objectionable. More specifically, a process and associated product is described herein, comprising applying a solution of hop extract to a food, beverage or other medium so that the final concentration of hop ingredients is about 1 ppm or higher in order to inhibit the growth of Clostridium botulinum, Clostridium difficile, and/or Helicobacter pylori.

Abstract: This invention relates to polymer production and in particular to a novel copolymer and a process for microbiologically producing the same. More specifically this invention provides for a poly-3-hydroxyalkanoate (PHA) that includes medium length 3-hydroxyacyl monomers and a process comprising culturing a microorganism with a medium chain fatty carbon source and a fatty acid oxidation inhibitor. This invention allows the use of microorganisms which normally incorporate only short chain fatty acids to produce PHAs containing short and medium chain 3-hydroxyacyl monomers. The purpose of this invention is to produce a more versatile PHA polymer which includes C6, C7 and/or C8 3-hydroxyacyl monomers.

Abstract: Novel multicomponent clostridial vaccine formulations using readily dispersible, non-depot adjuvants, such as saponin, are disclosed. The vaccines can be administered to cattle intramusculary or subcutaneously without the severe persistent local reactions, such as granulomas, abscesses, and scarring, normally seen with other multicomponent clostridial vaccines.

Abstract: The present invention provides a method for the use of at least one serotype or a combination of serotypes of Botulinum neurotoxin either alone or in combination with other peptides or fusion proteins, that when administered in a safe and effective amount, antagonize and therefore decrease or block inflammation induced by the neurogenic mechanisms underlying or associated with inflammatory disorders, in particular, arthritis.

Abstract: The invention describes a process for the preparation of .delta.-decalactone or .delta.-dodecalactone by the hydrogenation of 2-decen-5-olide and 2-dodecen-5-olide, or a derivative therof, by a bacteria capable of effecting said hydrogenation, preferably by a bacteria of the Clostridium genus. In an embodiment of the invention, 5-hydroxy-2-decenoic acid or 5-hydroxy-2-dodecenoic acid is used as substrate in the hydrogenation reaction.

Abstract: A label-based assay is described, through modifications of substrate strure and derivatization of serum albumin, which can be used to determine type A proteolytic activity without separation of products.

Abstract: A hybrid botulinal neurotoxin is disclosed. In one embodiment, the neurotoxin comprises a combination of a botulinal neurotoxin heavy chain and light chain, wherein the light chain and heavy chain are not of the same serotype. A method for creating hybrid neurotoxins comprised of different functional domains is also disclosed.

Abstract: An enzyme preparation that exhibits cephalosporin haloperoxidase activity is isolatable from a microorganism species of the Rathayibacter genus. This enzyme preparation can convert cephalexin to a halogenated cephalosporin antibiotic in a single step. A particular, unique microorganism that can provide the cephalosporin haloperoxidase enzyme preparation is Rathayibacter biopuresis.

Abstract: A novel compound, 12,13,17-trihydroxy-9(Z)-octadecenoic acid (THOA) was produced from linoleic acid by microbial transformation at 25% yield. The newly isolated microbial strain catalyzing this transformation was identified as Clavibacter sp. ALA2 (Accession No. NRRL B-21660). THOA and its derivatives have application as antifungal agents.

Abstract: The isolation and purification of type G botulinum neurotoxin and complexes thereof is disclosed. Compositions containing the type G neurotoxin and the preparation of a type G toxoid are also disclosed.

Abstract: The instant invention describes a process for the manufacture of butanol and like volatile organic compounds by fermenting carbohydrates, mainly polysaccharide, with micro-organisms which convert carbohydrates into mainly butyric acid and other acids. The acids are subsequently transferred to the solventogenesis production stage using a different strain of bacteria which continuously produces butanol and like volatile organic compounds, via a multistage fermentation process that is stable, high yielding (weight product per unit weight carbohydrates) and productive (faster throughput). By employing one microbe (the first) in the major pathway to produce the acid of choice specifically and faster, and provide for another microbe (the second) with the unique property to convert the acid to a solvent, carbohydrates are not wasted on ancillary product. The unique advantage of the second microbe is that it has the capability of converting acids into solvents (solventogenesis).

Abstract: Clostridium thermocellum biovar. nov. SK522 (FERM BP-345 g) is a thermophilic cellulose decomposing bacteria, capable of solubilizing lignin and fermenting cellulose excellently. Although its temperature limit for growth is 40.degree.-80.degree. C., it grows best at 65.degree.-72.degree. C.Thermus aquaticus biovar. nov. SK542 (FERM BP-3382) is an absolute aerobic bacteria. It grows at temperature limit of 40.degree.-82.degree. C. in a normal concentration medium, but its best growth is achieved at 72.degree.-76.degree. C. It produces protein decomposing enzymes functional at a temperature of 75.degree.-85.degree. C. and active in a wide pH range of 4.0-11.3, and a yellow pigment of carotenoid groups.Both strains can be mix-cultured. Depending on various purposes, as the mix culture is able to decompose organic materials containing cellulose and/or lignin, it can be used for soil improvement.

Abstract: A method for testing causative bacterial species of food poisoning which is characterized by using two oligonucleotide primers that hybridize to opposite strands of bacterial DNA specifically, and flank a unique region in the target DNA and amplifying the specific fragment of the bacterial DNA, comprising the steps of:(a) hybridizing the primer to specific gene sequence of bacteria in a sample, extending the hybridized primer with deoxynucleotide triphosphates (dATP, dCTP, dGTP, and dTTP), and resultantly making the double strand nucleotide;(b) where the primer extension products are cleaved into each single strand of nucleotide by certain external force such as heat, pH and so on, one single strand functioning as a template for nucleotide extension with a primer of the other strand;(c) repeating a series of cycles involving cleavage of primer extension products, primer hybridizing, extension of the hybridized primers to amplify the specific fragment of DNA, and detecting the amplified DNA fragment; and(d) as

Abstract: Novel cyclodextrin glycosyl transferases (CGTase) can be produced by anaerobic cultivation of strains of Thermoanaerobacter or Thermoanaerobium. They are more thermostable than known CGTases and have temperature optimum about 95.degree. C.The novel CGTases can be used for starch liquefaction at pH 4.5 and temperature exceeding 100.degree. C. in the production of dextrose or ethanol. They can also be used for conversion of liquefied starch to cyclodextrin at a temperature of 80.degree.-90.degree. C.A method for enzymatically converting solid and liquefied starch into cyclodextrin using cyclodextrin glycosyl transferases (CGTase) elaborated by thermophilic obligate anaerobic strains belonging to the genus Clostridium. These CGTases are characterized by thermostability and a capability to liquefy starch and/or to convert liquefied starch to cyclodextrin at pH 5.0-5.5 and 60.degree.-90.degree. C.

Abstract: The invention is directed to biological processes and apparatus for determining the efficacy of a sterilization cycle based upon the recovery of activity of interactive enzyme systems comprising enzymes, coenzymes, catalysts, cofactors, substrates or any other necessary reagents. The invention provides a vital process for expediting sterility verification before utilization of the articles thought to be sterilized. The invention involves the rapid detection of any surviving interactive enzymatic activity which directly relates to the probability of any biological spores surviving in a test sample. An absence of a change indicates that the sterilization process had inactivated the enzyme system thereby preventing the interactive reaction from taking place which is a rapid equivalent to directly detecting the survivability of bacterial spores in a similar test.

Abstract: There are described a novel protein derived from Clostridium perfringens FERM BP-4584 method of obtaining the same and use thereof as an effective ingredient for treating wounds and ulcers. The protein has a molecular weight of 420,000.+-.40,000 by a GPC, isoelectric point of 4.8, and consists of a single subunit having a molecular weight of 130,000.+-.20,000 by a SDS-polyacrylamide gel electrophoresis, and shows cell growth-stimulating activity as well as macrophage chemotactic action. The protein can be extracted and separated by conventional techniques for obtaining a protein from general microorganisms, by taking an inhibition of decomposition into consideration, since the protein is not so stable.

Abstract: The present invention relates to a process for preparing hydrogen gas on an industrial scale by culturing the microorganism Clostridium beijerinckii Ferm BP-3592 or the anaerobic asporogenic bacterium strain Ferm BP-3593 in a medium containing glucose and/or a polysaccharide containing a glucose unit.

Abstract: The present invention relates to a process for preparing hydrogen gas on an industrial scale by culturing the microorganism Clostridium beijerinckii Ferm BP-3592 or the anaerobic asporogenic bacterium strain Ferm BP-3593 in a medium containing glucose and/or a polysaccharide containing a glucose unit.

Abstract: A process for the preparation of optically pure diastereoisomers of tetrahydrofolate compounds is described, comprising the conversion, for example, of only the 5,6S,7,8-tetrahydrofolic acid component of a racemic mixture of 5,6,7,8-tetrahydrofolic acid to 10-formyl-5,6S,7,8-tetrahydrofolic acid in the presence of a formyl tetrahydrofolate synthetase, followed by cyclizing, hydrolyzing and derivatizing. The process is also useful to make a desired substantially pure (6R or 6S) enantiomer of a derivative of (radiolabeled) tetrahydrofolic acid or a salt or ester thereof.

Abstract: A process for purifying crude collagenase is disclosed. The collagenase purification process includes providing a stabilized crude collagenase solution containing collagenase, pigment, toxins, bacterial materials, and proteolytic enzyme impurities including clostripain, trypsin, and caseinase. The stabilized collagenase solution is applied to hydroxylapatite packing. pigment and caseinase are eluted with a first solution comprising about 0.05 M to about 0.3 M phosphate buffer, and then collagenase, trypsin, and clostripain are eluted with a second solution comprising about 0.35 M to about 0.5 M phosphate buffer to provide a first collected solution. The first collected solution is then applied to gel filtration packing and collagenase and clostripain are eluted with a neutral pH buffer solution, to provide a second collected solution. The second collected solution is then applied to Reactive Red 120-Agarose packing and collagenase is eluted with a neutral pH buffer solution to provide purified collagenase.

Abstract: The invention provides a method for the growth promotion of animals, comprising orally administering into animals killed microbial cells of bacteria belonging to the genus Clostridium, and also provides a powder composition, which comprises as essential ingredients killed microbial vegetative cells of bacteria belonging to the genus Clostridium, together with saccharides and/or starches.

Abstract: A preventive and curative medical composition for Clostridium difficile diarrhea and psedomembranous colitis, which composition comprises cells or spores of a butyric acid bacterium and Vancomycin.

Abstract: A genetically engineered glucose isomerase with improved affinity for D-glucose and the method of preparation of such a glucose isomerase are disclosed. The glucose isomerase is obtained by mutagenizing the gene of a naturally occurring glucose isomerase such that a smaller amino acid replaces a larger amino acid in the catalytic site. In an especially advantageous embodiment of the present invention, the Clostridium glucose isomerase sequence is mutated and the residue replaced with a smaller amino acid is either Trp.sub.139 or Val.sub.186.

Abstract: A process for the manufacture of alkaline earth salts of acetic acid. Biomass is fermented under appropriate conditions to produce acetic acid, which is extracted from the fermentation broth with the aid of a basic liquid ion exchanger dissolved in an organic phase. The organic phase containing the product acetic acid is then reacted directly with a basic material such as limestone, and the resulting alkaline earth acetate product is recovered from the aqueous phase.

Abstract: A process for the transformation of glycerol into 1,3-propanediol by microorganisms comprising fermenting the microorganisms in media having a glycerol content of from about 5% to about 20% by weight under standard anaerobic fermentation conditions and recovering the 1,3-propanediol. The microorganisms according to the invention do not suffer catabolic repression by the large amount of 1,3-propanediol produced by the process.

Abstract: A mutant of bacterium Clostridium histolyticum, designated Clostridum histolyticum K26 clo 88 of the following characteristics: the lack of a motility system which is a fundamental characteristic of the parenteral strain; and, the inability to biosynthesize the accompanying enzyme clostripain. A process of obtaining the above mutant and its use in a process for the production of clostripain-free collagenase are also provided.