Abstract: The present invention provides an improved method for the manufacture of Mycophenolic acid by solid substrate fermentation of Pencillium brevi-campactum, in a contained bioreactor under optimal fermentation parameters with its subsequent purification steps.

Abstract: A method for enzymatically synthesizing a polymer by combining a preselected quantity of an enzyme, a first reactant selected from polymers with at least one carboxylic acid pendant group, a second reactant selected from alcohols, i.e., polyols, in a reaction vessel; heating the reaction vessel to a preselected temperature; and maintaining the reaction vessel at the preselected temperature for a preselected time with mixing, wherein an esterification reaction results at at least one carboxylic acid pendant group of the polymer with one hydroxyl group from the polyol and results in a modified polymer.

Abstract: The present invention provides novel drechsleranol compounds of formula (I) which are formed by the microorganism Drechslera australlensis, ST 003360, DSM 14093, or a fungus ST 004112, DSM 14524, during fermentation. A process for their preparation, pharmaceutical compositions containing said drechsleranols their use for the treatment and/or prophylaxis of degenerative neuropathies, such as, Alzheimeu's disease, or psychiatric disorders, such as depression, sleep disturbance or seasonal affective disorder, and their use as chelating agents or antioxidants are also disclosed and claimed.

Abstract: The present invention relates to non-fermentative methods for the production of ASA intermediates, KDG, DKG and KLG and methods for the regeneration of co-factor. The invention provides genetically engineered host cells comprising heterologous nucleic acid encoding enzymes useful in the process.

Abstract: The invention relates to a process for the preparation of a 2,4-dideoxyhexose or a 2,4,6-trideoxyhexose from a substituted or unsubstituted carbonyl compound with at least 2 carbon atoms and at least one &agr;-hydrogen atom and a substituted or unsubstituted aldehyde in the presence of an aldolase and water, the reaction between the substituted or unsubstituted carbonyl compound with at least 2 carbon atoms and at least one &agr;-hydrogen atom and the substituted or unsubstituted aldehyde being carried out at a carbonyl concentration of at most 6 moles/l of reaction mixture and the final concentration of the 2,4-dideoxyhexose or the 2,4,6-trideoxyhexose being at least 2 mass % of the reaction mixture. The invention also relates to the use of a 2,4-dideoxyhexose or a 2,4,6-trideoxyhexose obtained by means of a process according to the invention in the preparation of a medicine, particularly in the preparation of a statine.

Abstract: A process for producing L-ascorbic acid or D-erythorbic acid, or in each case its sodium, potassium or calcium salt, from 2-keto-L-gulonic acid or 2-keto-D-gluconic acid, or in each case its sodium, potassium or calcium salt, that involves incubating 2-keto-L-gulonic acid or 2-keto-D-gluconic acid, each as the free acid or as its sodium, potassium or calcium salt, and the cells of a thermoacidophilic microorganism at temperatures from about 30° C. to about 100° C., and at a pH from about 1 to about 6, in a solution, to form L-ascorbic acid or D-erythorbic acid or an appropriate salt thereof, and isolating said product from the solution.

Abstract: The present invention provides methods for directing the evolution of microorganisms comprising the use of mutator genes and growth under conditions of selective pressure. The method discloses mutator genes which can be used in the methods of the present invention and provides ATCC deposits which exemplify the evolved microorganisms produced by the methods.

Abstract: There is provided a microbiological one-step method for the manufacture of ascorbic acid. The method comprises use of the operon expressing 2-ketogluconate dehydrogenase in naturally occurring microorganisms and microorganisms transformed with DNA encoding the 2-ketogluconate dehydrogenase gene. Ascorbic acid is obtained from culturing microorganisms expressing 2-ketogluconate dehydrogenase.

Abstract: A process is disclosed for preparing an (S)-2-amino-&ohgr;-oxoalkanoic acid derivative in which the corresponding aldehyde is converted into the corresponding acetal-protected aldehyde, the acetal-protected aldehyde is converted into the corresponding aminonitrile, the aminonitrile is converted into the corresponding amino acid amide, the amino acid amide is subjected to an enzymatic, enantioselective hydrolysis in which the (R)-enantiomer of the amino acid amide remains and the (S)-enantiomer is converted into the (S)-amino acid, and the (S)-amino acid is isolated. Preferably, the reaction mixture obtained after the conversion of the aminonitrile into the amino acid amide is treated with a benzaldehyde to form the Schiff base of the amino acid amide. The Schiff base is separated out and is converted into the free amino acid amide.

Abstract: Methods and compositions that can be used to make monatin from glucose, tryptophan, indole-3-lactic acid, indole-3-pyruvate, and 2-hydroxy 2-(indol-3-ylmethyl)-4-keto glutaric acid, are provided. Methods are also disclosed for produding the indole-3-pyruvate and 2-hydroxy 2-(indol-3-ylmethyl)-4-keto glutaric acid intermediates. Compositions provided include nucleic acid molecules, polypeptides, chemical structures, and cells. Methods include in vitro and in vivo processes, and the in vitro methods include chemical reactions.

Abstract: The present invention relates to a process for preparing optically pure (S)-3-hydroxy-&ggr;-butyrolactone expressed by the following Formula 1 and more particularly, to a process that enables preparing optically pure (S)-3-hydroxy-&ggr;-butyrolactone economically in large quantities, by: (a) Preparing &agr;-(1,4) linked oligosaccharide with adequate sugar distribution by reacting starch which is easily available from natural product with enzyme under a specific condition; and (b) Performing oxidation and cyclization sequentially under a specific condition.

Abstract: The present invention relates to the novel isolated 12-30 strain of Pestalotiopsis microspora capable of producing novel antioxidant and antimycotic agents. The present invention also relates to the novel isolated 3,5,7 trisubstituted isobenzofuranone and derivatives thereof, methods of isolating the novel isobenzofuranone from cultures P. microspora 12-30, and to novel uses of the compound as an antioxidant and antimycotic agent. The present invention further relates to a novel 1,5,7 trisubstituted 1,3-dihydroisobenzofuran and derivatives thereof, methods of isolating this novel compound from cultures of Pestalotiopsis microspora 12-30, and to uses thereof.

Abstract: The invention relates to a variant of a parent fungal glucoamylase, which exhibits altered properties, in particular improved thermal stability and/or increased specific activity.

Abstract: The present invention discloses sequence information relating to pyranosone dehydratase.

Abstract: The present invention provides means for the production of desired end-products of in vitro and/or in vivo bioconversion of biomass-based feed stock substrates, including but not limited to such materials as starch and cellulose. In particularly preferred embodiments, the methods of the present invention do not require gelatinization and/or liquefaction of the substrate.

Abstract: Described herein are novel nucleic acids, proteins and methods that can be used to provide new catalysts with desirable traits for industrial processes. In particular, novel reductases isolated from the environment using PCR methods are described.

Abstract: Herein is disclosed a method of generating ascorbic acid from yeast. In one embodiment, the yeast is a Zygosaccharomyces spp. or a Kluyveromyces spp. growing in a medium comprising an ascorbic acid precursor. In a second embodiment the yeast is a recombinant yeast growing in a medium comprising an ascorbic acid precursor. Preferably the recombinant yeast is transformed with a coding region encoding an enzyme selected from L-galactose dehydrogenase (LGDH), L-galactono-1,4-lactone dehydrogenase (AGD), D-arabinose dehydrogenase (ARA), D-arabinono-1,4-lactone oxidase (ALO) or L-gulono-1,4-lactone oxidase (RGLO). The ascorbic acid precursor is preferably D-glucose, L-galactose, L-galactono-1,4-lactone, or L-gulono-1,4-lactone. In another preferred embodiment the ascorbic acid is accumulated in the medium at levels greater than background. Preferably, the yield of the conversion of the precursor to ascorbic acid is preferably at least about 35%.

Abstract: The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from D-glucose is disclosed.

Abstract: A process for purifying and concentrating a gluconic acid derivative, such as 2-keto-L-gulonic acid, comprising introducing a non-viable and/or acidified fermentation medium or an in-vitro reactor medium comprising at least the gluconic acid derivative and/or salt thereof to electrodialysis thereby purifying and concentrating the gluconic acid derivative.

Abstract: The invention provides methods and host cells for the production of ascorbic acid intermediates. The invention also provides host cells having a modification in a polynucleotide that uncouples the catabolic pathway from the oxidative pathway by deleting the encoding for an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and/or a polynucleotide that has deleted the encoding for endogenous enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such host cells are used for the production of products, such as, ascorbic acid intermediates. Nucleic acid and amino acid sequences with inactivated enzymatic activity which phosphorylates D-glucose at its 6th carbon and inactivated enzymatic activity which phosphorylates D-gluconate at its 6th carbon are provided.

Abstract: The invention relates to a means for enhancing the value of distillation residues of fermentation products and in particular, a process for producing compounds of economic interest from these distillation residues of fermentation products. This production process also comprises suitable steps for extracting these compounds. In particular, the invention relates to enhancing the value of distillation residues of fermentation products from the agro-feeding industry.

Abstract: A process for large-scale, low cost, batch or continuous production of polyphenols using enzyme-mediated reactions and methods for recycling non-consumed reactants.

Abstract: Biocatalysis is used to prepare 4-hydroxy-3[2H]-furanones from substituted benzenes. A substituted benzene is enzymatically oxidized to form a diol-diene compound, which is then oxidized and cyclized to form a 4-hydroxy-3[2H]-furanone. Dioxygenases are used to perform the enzymatic oxidation. In addition, methods of obtaining improved dioxygenases are provided. Compositions including one or more of the intermediate compounds in the biocatalysis method, the resulting 4-hydroxy-3[2H]-furanone compounds, and improved enzymes are also provided.

Abstract: This invention relates to the isolation of a novel putative efflux gene from Pseudomonas mendocina. The putative efflux gene is useful for probing an organism's efflux system to gain an understanding of the mechanisms of solvent tolerance. The invention further provides a Pseudomonas mendocina strain deficient in this gene. This strain is unable to grow in the presence of chloramphenicol and, compared to the wildtype strain, grows slowly in the presence of high concentrations of PHBA.

Abstract: The present invention provides for the production of ASA from yeast capable of producing ASA from KLG. The present invention provides methods for the production of ASA as well as recombinant yeast capable of producing ASA from a carbon source.

Abstract: A process for preparing an optically active 4-halogeno-1,3-butanediol and (R)-1,2,4-butanetriol or (S)-3-hydroxy-&ggr;-butyrolactone which comprises reacting a racemic 4-halogeno-1,3-butanediol with a specific microorganism belonging to the genus Pseudomonas.

Abstract: The invention relates to a method for the enantioselective reduction of 3,5-dioxocarboxylic acid derivatives and their syntheses. According to the invention, compounds of formula (4) are reacted with an alcohol dehydrogenase which preferably stems from Lactobacillus brevis and which is recombinantly over-expressed in Escherichia coli, in the presence of NADPH. The keto group in position 5 is enantioselectively reduced during this reaction. The keto group in position 3 can also be specifically syn- or anti-reduced in a further step by means of chemical or enzymatic reactions.

Abstract: The present invention relates to novel bacterial strains belonging to the genera Gluconobacter, Ketogulonogenium and Bacillus useful for the production of 2-keto-L-gulonic acid. The present invention further relates to the use of these strains for the production of 2-keto-L-gulonic acid in mixed culture by fermentative conversion of D-sorbitol. The present invention further relates to the strains of the present invention transformed by a vector.

Abstract: Disclosed is a method for optically resolving a racemic &agr;-substituted heterocyclic carboxylic acid (&agr;-HCCA) by taking advantage of enantioselectivity of enzymes. &agr;-HCCA is reacted with alcohol to give a racemic &agr;-HCCA ester, which is then reacted with an enzyme with enantioselectivity, whereby either R-form or S-form of the racemate is hydrolyzed. Extraction with an organic solvent can obtain enantiomers of the &agr;-HCCA ester. The extracted enantiomeric &agr;-HCCA ester is converted to enantiomeric &agr;-HCCA by catalytic hydrogenation in an organic solution or by enzymatic hydrolysis in an aqueous solution. Thus, a racemic mixture of &agr;-HCCA can be optically resolved with high optical purity at high yields as well as at low cost.

Abstract: Disclosed is a method for preparing an R- or S-forms of &agr;-substituted heterocyclic carboxylic acid (&agr;-HCCA) and a counter enantiomeric form of &agr;-substituted heterocyclic carboxylic acid ester thereto by use of an enzyme. A racemic &agr;-HCCA is reacted with alcohol to give a racemic &agr;-HCCA ester, which is then brought into contact with an enzyme with enantioselectivity, whereby either R-form or S-form of the racemate is hydrolyzed. Extraction with an organic solvent can obtain enantiomers of the &agr;-HCCA ester. Thus, a certain enantiomeric form of &agr;-HCCA and a counter enantiomeric form of &agr;-HCCA ester thereto, respectively can be prepared with high optical purity at high yields as well as at low cost.

Abstract: The present invention relates to a process for the production of 2-keto-L-gulonic acid by fermentative conversion of L-sorbose and/or D-sorbitol. The present invention further relates to novel bacterial strains useful in this process.

Abstract: The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from D-glucose is disclosed.

Abstract: The present invention relates to a continuous process for preparing optically pure (S)-3-hydroxy-&ggr;-butyrolactone expressed by the following Formula 1 and more particularly, to a process which enables preparing optically pure (S)-3-hydroxy-&ggr;-butyrolactone economically in large quantities, by: (a) Preparing &agr;-(1,4) linked oligosaccharide with adequate sugar distribution by reacting amylopectin which is easily available from natural product with enzyme under a specific condition; and (b) Performing oxidation, esterification and cyclization sequentially under a specific condition.

Abstract: The invention provides a process for the recovery of erythorbic acid from an aqueous feed solution containing values of erythorbic acid at a concentration of less than 0.7 mol/kg, comprising extracting said erythorbic acid with a water-immiscible organic extractant composition comprising at least one secondary or tertiary alkyl amine in which the aggregate number of carbon atoms is at least 20, as a primary extractant, and a polar extraction enhancer compound; wherein said extractant composition comprises at least 2 moles of said polar extraction enhancer compound per one mole of primary extractant; separating said erythorbic acid-containing organic extractant composition from residual aqueous solution, and subjecting said erythorbic acid-containing organic extractant composition to a stripping operation with aqueous solution at a temperature of at least 20° C.

Abstract: A process for producing L-ascorbic acid (vitamin C) from 2-keto-L-gulonic acid or D-erythorbic acid from 2-keto-D-gluconic acid by contacting 2-keto-L-gulonic acid or 2-keto-D-gluconic acid, respectively, in solution with a lactonase, particularly one belonging to the enzyme class EC 3.1.1.x, according to the classification of Enzyme Nomenclature. The solvent for this reaction can be water, an aqueous alcohol, a non-alcoholic organic solvent or a mixture of an aqueous alcohol and a non-alcoholic organic solvent. The contacting is generally performed in a temperature range of 0.degree. C. to 120.degree. C. and a pH range of 1.5 to 12. In each case the starting material can be in the form of the free acid, the sodium salt, or the calcium salt. The so-produced vitamin C has very well known uses, and the alternatively produced D-erythorbic acid is useful as an antioxidant for food additives.

Abstract: Disclosed is a process for preparing novel trans-3-alkyloxy-4-hydroxytetrahydrofurans including racemic and substantially enantiomerically pure (3S,4S)-trans-3-alk(en)yloxy-4-hydroxytetrahydrofurans and (3R,4R)-trans-3-alk(en)yloxy-4-acyloxytetrahydrofurans. The disclosed process comprises the steps of reacting 3,4-epoxytetrahydrofuran with an alcohol under Lewis acid catalysis to obtain a racemic trans-3-alk(en)yloxy-4-hydroxytetrahydrofuran; contacting the trans-3-alk(en)yloxy-4-hydroxytetrahydrofuran with an acyl donor in the presence of a hydrolase enzyme to produce a mixture of a substantially enantiomerically pure (3S,4S)-trans-3-alk(en)yloxy-4-hydroxytetrahydrofuran and a substantially enantiomerically pure (3R,4R)-trans-3-alk(en)yloxy-4-acyloxytetrahydrofuran; and separating the components of the mixture by partitioning between water and a solvent immiscible with water.

Abstract: A process is disclosed for preparing an (S)-2-amino-.omega.oxoalkanoic acid derivative in which the corresponding aldehyde is converted into the corresponding acetal-protected aldehyde, the acetal-protected aldehyde is converted into the corresponding aminonitrile, the aminonitrile is converted into the corresponding amino acid amide, the amino acid amide is subjected to an enzymatic, enantioselective hydrolysis in which the (R)-enantiomer of the amino acid amide remains and the (S)-enantiomer is converted into the (S)-amino acid, and the (S)-amino acid is isolated. Preferably, the reaction mixture obtained after the conversion of the aminonitrile into the amino acid amide is treated with a benzaldehyde to form the Schiff base of the amino acid amide. The Schiff base is separated out and is converted into the free amino acid amide.

Abstract: The present invention relates to a process for preparing optically pure (S)-3-hydroxy-.gamma.-butyrolactone expressed by the following Formula 1 and more particularly, to a process that enables preparing optically pure (S)-3-hydroxy-.gamma.-butyrolactone economically in large quantities, by:(a) Preparing .alpha.-(1,4) linked oligosaccharide with adequate sugar distribution by reacting amylopectin which is easily available from natural product with enzyme under a specific condition; and(b) Performing oxidation, esterification and cyclization sequentially under a specific condition.

Abstract: A process for producing high yields of .gamma.-hexalactone and 2-pentanone from the corresponding hexanoic acid starting material is carried out with high amounts of oxygen and sugar in the presence of a mold microorganism. Fragrance compositions and foodstuff compositions are augmented and enhanced by the presence of the product compounds.

Abstract: The present invention relates to a process for the preparation of a composition rich in sotolon from a source rich in 4-hydroxy-L-iso-leucine.

Abstract: Processes for preparing spirolaxine and spirolaxine methyl ether, the compounds of formulas (I) and (II) respectively, ##STR1## comprising fermenting fungi selected from the group consisting of Sporotrichum pruinosum FD 29585, ATCC 74327; Sporotrichum pruinosum FD 29454, ATCC 74329; Sporotrichun pruinosum FD 29586, ATCC 74328; and Phanerochaete chrysosporiun LN 3576, ATCC 74326. This invention also relates to a process for preparing spirolaxine comprising fermenting Sporotrichum pruinosum FD 29458, ATCC 74330.

Abstract: The invention provides an extraction process for the recovery of ascorbic id from an aqueous feed solution containing the acid at a concentration of less than 0.7 mol/kg.

Abstract: A method for purifying sclareolide comprises a separation step wherein debris, e.g., microbial cell debris is removed, and further comprises extracting an organic solution of sclareolide with an acid solution, followed by an extraction of the partially purified sclareolide with a basic solution, thus yielding sclareolide of very high purity.

Abstract: The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from D-glucose is disclosed.

Abstract: This invention provides processes for producing phthalide compounds which comprise cultivating Phanerochaete avelutina FERM BP-4787 and then isolating phthalide compounds from the fermentation broth.

Abstract: The invention provides a process for the recovery of erythorbic acid from an aqueous feed solution containing values of erythorbic acid at a concentration of less than 0.7 mol/kg, comprising adsorbing a major portion of said erythorbic acid with a solid phase adsorbent resin selected from resins carrying a pyridine function and resins of similar or weaker basicity; separating said erythorbic acid-containing resin from residual aqueous solution, and subjecting said erythorbic acid-containing resin to a desorbing operation with a neutral solvent at a temperature of at least 20.degree. C. higher than the temperature at which said adsorption is carried out, whereby there is obtained a solution of erythorbic acid in solvent in which the concentration of erythorbic acid is at least equal to its concentration in said aqueous feed solution.

Abstract: The present invention concerns novel compounds obtained by fermenting a microorganism of the genus Memnonoiella or Stachybotrys, which compounds are inhibitors of the enzyme inositol monophosphatase (EC 3.1.3.25). The present invention also relates to the use of these novel compounds in treating manic depression and pharmaceutical formulations comprising said compounds as active ingredient; a further object is the use of these compounds in an analytical method for detecting inositol monophosphatase.

Abstract: A microbiological process for the production of .gamma.-decalactone. According to this process, a culture of the fungus of a particular species of the genus Mucor is incubated with the particular substrate, which is an organic carboxylic acid ester, to produce fermentatively the .gamma.-decalactone. Exact conditions have now been discovered under which .gamma.-decalactone can be prepared in high yields. These conditions are based upon the fermentative incubation of a fungus of the genus Mucor in conjunction with the appropriate substrate in order to obtain the high yield of the desired lactone.

Abstract: The present invention relates to a process for the production of 2-keto-L-gulonic acid by fermentative conversion of L-sorbose and/or D-sorbitol. The present invention further relates to novel bacterial strains useful in this process.

Abstract: The present invention relates to a novel process for the preparation of citraconic anhydride. More precisely, the invention relates to a process for the preparation of citraconic anhydride from a starting material comprising itaconic acid.The process for the preparation of citraconic anhydride may be performed continuously starting from itaconic acid, or continuously or in a batchwise manner starting directly from a fermentation broth of itaconic acid or of by-products from the manufacture of itaconic acid.