Abstract: The invention relates to the microbial synthesis of polyhydroxyalkanoic acids [PHA(B)] from substrates which have potential environmental toxicity and must therefore be detoxified and which, if capable of being utilized as a source of carbon and energy by microorganisms for growth and propagation, exhibit the phenomenon of substrate inhibition. According to the invention, a process for the continuous microbiological production of PHB is provided, which process is characterized in that strains of microorganisms known to be PHB producers are propagated chemo-statically at maximum heat production on substrates exhibiting growth inhibition in case of excess substrate, the maximum heat production corresponding to a maximum PHB content in the biomass being adjusted by means of the substrate flow rate.

Abstract: The present invention provides several methods for biological production of para-hydroxycinnamic acid (PHCA). The invention is also directed to the discovery of new fungi and bacteria that possess the ability to convert cinnamate to PHCA. The invention relates to developing of a new biocatalyst for conversion of glucose to PHCA by incorporation of the wild type PAL from the yeast Rhodotorula glutinis into E. coli underlining the ability of the wildtype PAL to convert tyrosine to PHCA. The invention is also directed to developing a new biocatalyst for conversion of glucose to PHCA by incorporation of the wildtype PAL from the yeast Rhodotorula glutinis plus the plant cytochrome P-450 and the cytochrome P-450 reductase into E. coli. In yet another embodiment, the present invention provides for the developing of a new biocatalyst through mutagenesis of the wild type yeast PAL which possesses enhanced tyrosine ammonia-lyase (TAL) activity.

Abstract: This invention relates to a process for the preparation of a 3-hydroxycarboxylic acid from a 3-hydroxynitrile. More specifically, 3-hydroxyvaleronitrile is converted to 3-hydroxyvaleric acid in high yield at up to 100% conversion, using as an enzyme catalyst 1) nitrile hydratase activity and amidase activity or 2) nitrilase activity of a microbial cell. 3-Hydroxyvaleric acid is used as a substitute for &egr;-caprolactone in the preparation of highly branched copolyester.

Abstract: The very effective conversion of ML-236B substances and derivatives thereof into 6′-hydroxylated products with the microorganisms of species Amycolatopsis orientalis, or with an extract or a hydroxylation-effective enzyme derived from said microorganism, is described. The products obtained are suitable as HMG-CoA reductase inhibitors or intermediates thereof. Thus, the products can be used, for example, as an antihypercholesterolemic in pharmacy.

Abstract: A method is provided for isolating and purifying PHA from microbial or plant biomass that contains PHA. The method includes the step of extracting PHA from the biomass using at least one solvent while simultaneously subjecting the biomass to a filtration process to remove cells. In a preferred embodiment of the method, an aqueous slurry of the biomass is directly extracted by diafiltration using an organic solvent. In a preferred diafiltration process, an aqueous slurry of microbial cells comprising PHA is recirculated through a filtration membrane, wherein the membrane has a pore size sufficiently small to reject individual cells or such aggregates of cells as may exist in the slurry.

Abstract: The present invention provides several methods for biological production of para-hydroxycinnamic acid (PHCA). The invention is also directed to the discovery of new fungi and bacteria that possess the ability to convert cinnamate to PHCA. The invention relates to developing of a new biocatalyst for conversion of glucose to PHCA by incorporation of the wild type PAL from the yeast Rhodotorula glutinis into E. coli underlining the ability of the wildtype PAL to convert tyrosine to PHCA. The invention is also directed to developing a new biocatalyst for conversion of glucose to PHCA by incorporation of the wildtype PAL from the yeast Rhodotorula glutinis plus the plant cytochrome P-450 and the cytochrome P-450 reductase into E. coli. In yet another embodiment, the present invention provides for the developing of a new biocatalyst through mutagenesis of the wild type yeast PAL which possesses enhanced tyrosine ammonia-lyase (TAL) activity.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of HsKif9, antibodies to HsKif9, methods of screening for HsKif9 modulators using biologically active HsKif9, and kits for screening for HsKif9 modulators.

Abstract: Process for the preparation of optically highly pure (R)— and (S)—&agr;-hydroxycarboxylic acids, in which either isolated, impure (R)— and (S)—&agr;-hydroxycarboxylic acids prepared by acidic hydrolysis of the (R)— and (S)—cyanohydrins obtained by enzyme-catalyzed addition of a cyanide group donor to the corresponding aldehydes or ketones are recrystallized in an aromatic hydrocarbon, optionally in the presence of a cosolvent, and optically highly pure (R)— and (S)—&agr;-hydroxycarboxylic acids having an optical purity of over 98%ee are obtained or the hydrolysis solution obtained by acidic hydrolysis of the (R)— and (S)—cyanohydrins is treated directly with an aromatic hydrocarbon, optionally in combination with a cosolvent, and is then extracted at hydrolysis temperature, whereupon after cooling of the organic phase the corresponding chemically and optically highly pure (R)— and (S)—&agr;-hydroxycarboxylic acids having an optical purity

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: The present invention relates to a process for preparing optically pure (S)-3,4-dihydroxybutyric acid derivatives expressed by the following Formula 1 and more particularly, to a process that enables preparing optically pure (S)-3,4-dihydroxybutyric acid derivatives 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 and esterification sequentially under a specific condition. wherein, R represents linear or branched alkyl group with 1˜5 carbon atoms.

Abstract: The cloning and expression of genes in the common aromatic pathway of E. coli are described. A compound for which chorismate, the final product of the common aromatic pathway, is an anabolic intermediate can be produced by cloning and expressing selected genes of the common aromatic pathway and the genes coding for enzymes necessary to convert chorismate to the selected compound. Plasmids carrying selected genes of the common aromatic pathway are also described.

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: This invention relates to a biocatalytic process to produce terephthalic acid and isophthalic acid from p-xylene and m-xylene, respectively. Terephthalic acid has been prepared by oxidizing p-xylene with bacteria belonging to the genus Burkholderia. Conversion of p-xylene into terephthalic acid is accomplished by a single bacterial strain that produces all of the requisite enzymes. In addition, this invention relates to the preparation of isophthalic acid from a mixture of m- and p-xylene.

Abstract: Method for the production of vanillic acid and vanillin by bioconversion from ferulic acid in a medium containing phospholipids cultured with at least one microorganism from the classes Ascomycetes, Basidiomycetes or Actinomycetes. Vanillin is also produced by bioconversion of vanillic acid by at least one microorganism of the class Basidiomycetes in a medium containing cellobiose.

Abstract: An amidase or nitrilase is made by continuous culture under carbon limitation using a carbon source which includes, respectively, either (a) an amide or amide precursor or (b) a nitrile or nitrile precursor. Novel enzymes have particular stability. A novel microorganism is Rhodococcus rhodochrous NCIMB 40756 and is capable of producing a particularly stable amidase. The novel amidase, and the amidase made by the defined process, are effective for converting (meth)acrylamide to ammonium (meth)acrylate, for instance in or after the polymerisation of the acrylamide.

Abstract: The PHA biosynthetic pathway is combined with a succinic semialdehyde metabolic pathway that metabolizes succinic semialdehyde via a 4-hydroxybutyryl-CoA intermediate in order to produce high levels of PHA comprising 4HB monomer units. This combination is particularly useful, in part, because the PHA biosynthetic pathway is well known and has been expressed to produce P(3HB) to levels as high as 70-80% of the cell dry weight, while the succinic semialdehyde metabolic pathway is also well known, and the combination of the two pathways means that production of PHAs comprising 4HB monomer units does not depend on immediate precursors of 4-hydroxybutyrate. Rather, the production of the PHAs comprising 4HB monomer units can occur simply from the extraction of succinate or succinyl-CoA from the citric acid cycle when the host cell is grown on an inexpensive carbon source such as glucose.

Abstract: This invention pertains to a method of production of 4-hydroxybenzoic acid, with purification and recovery of 4-hydroxybenzoic acid directly from the fermentation medium of a cultured organism, in the presence of other chemical species. Ion exchange resin is used during the fermentation process to recover the chemical product without the necessity of separating the biomass from the fermentation supernatant by filtration after fermentation is complete and then treating the filtrate to recover the product. This reduces or eliminates the need for filtration steps and eliminates the need for energy-intensive water removal processes. Furthermore, the removal of the product during the fermentation dramatically increases the production of the product during the fermentation process. This method therefore can both increase the amount of product produced in a single fermentation run and reduce the per unit cost of its biocatalytic production.

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: A fortified enzyme preparation of the gorgonian Pseudopterogorgia americana or Pseudopterogorgia elisabethae has been developed which efficiently transforms a variety of precursor molecules, e.g., sterols, to their corresponding metabolites, e.g., 9(11)-secosteroid in high yield. NAD, NADP, and glutamate dehydrogenase can be used as additives in this enzymatic conversion. In addition to naturally-occurring metabolites, novel secosteroids have been prepared.

Abstract: An enzymatic hydroxylation process for the preparation of compounds useful as HMG-CoA reductase inhibitors and/or as intermediates in the preparation of HMG-CoA reductase inhibitors uses a microorganism or an enzyme derived from, or having the structure of an enzyme derived from, said microorganism, which is capable of catalyzing the hydroxylation process.

Abstract: Polyhydroxyalkanoate (PHA) polyester is extracted from biomass by dissolving the PHA in a non-halogenated solvent which comprises a PHA-good solvent or a mixture thereof. Suitable PHA-good solvents can be selected from the disclosed alcohols, esters, amides and ketones. The PHA can be recovered, for example, by cooling, by solvent evaporation, or by addition of a PHA-poor solvent, wherein the PHA-poor solvent preferably dissolves less than about 1% (w/v) of the PHA at a temperature below the solvent boiling point. Preferred PHA types for use in the invention are poly (hydroxybutyrate-co-hydroxyvalerate), poly(3-hydroxybutyrate-co-4-hydroxybutyrate), and polymers/copolymers of hydroxyterminated polyhydroxybutyrate.

Abstract: A process for preparing .alpha.-hydroxy acids represented by the general formula (II): RCH(OH)COOH (wherein R represents a hydrogen atom, an optionally substituted C1-C6 alkyl group, an optionally substituted C2-C6 alkenyl group, an optionally substituted C1-C6 alkoxy group, an optionally substituted aryl group, an optionally substituted aryloxy group, or an optionally substituted heterocyclic group) by allowing a microorganism to act on .alpha.-hydroxy nitriles (I): RCH(OH)CN (wherein R is as defined above) to hydrolyze and convert the .alpha.-hydroxy nitrites to .alpha.-hydroxy acids (II), wherein the .alpha.-hydroxy acids (II) are produced and accumulated in an aqueous solvent by a microorganism having the concentration resistance to the .alpha.-hydroxy nitrites (I) and/or .alpha.-hydroxy acids (II) and durability preferably in the presence of a cyanide, and harvested. According to this process, the use of the microorganism having the concentration resistance to the .alpha.-hydroxy nitriles (I) and/or .

Abstract: The present invention pertains to a method for economical biofermentative production of 4-hydroxybenzoic acid (PHB) using genetically engineered E. coli. According to the invention, a plasmid is provided which controls the overexpression of chorismate pyruvate lyase, the bacterial enzyme which catalyzes the production of PHB from chorismate. Mutant E. coli selected with a unique two-step screening assay to overproduce chorismate have been transformed with this plasmid, providing a biocatalyst that efficiently converts glucose to PHB.

Abstract: Ferulic acid, vanillic acid, coniferyl alcohol and coniferyl aldehyde can be prepared from eugenol with the aid of a new Pseudomonas species.

Abstract: Strains of Aureobasidium pullulans (de bary) Arnaud can be used for the commercial production of gluconic acid by fermentation in aqueous liquid containing sugar, which in continuous culture from glucose form greater than or equal to 90% and greater than or equal to 90% molar selectivity. The process is conducted with an Fe and Mn optimized medium with a nitrogen-independent (N-independent) ion concentration. The iron (Fe) concentration with 3 g/l NH.sub.4 Cl is greater than or equal to 0.5 mM, and the manganese (Mn) concentration with 3 g/l NH.sub.4 Cl is greater than or equal to about 0.5 mM manganese (Mn). The pH is regulated between about 4.5 and about 8, in particular at 6.5-7, and the temperature between 24 and 32.degree. C., in particular at 29-30.degree. C. Particularly successful strains are Aureobasidium pullulans (de bary) Arnaud with the registration numbers DSM 7085, DSM 7086, DSM 7087, and DSM 7088.

Abstract: The present invention relates to a novel process for the preparation, by fermentation, of compounds of the formula I ##STR1## where R.sup.1 is hydrogen, fluorine, chlorine or bromine.

Abstract: A process of recovering PHA from a suspension which comprises particles of PHA in a liquid which comprises maintaining the suspension at a temperature at which the PHA melts and substantial coalescence of PHA particles occurs thereby at least partly forming a layer of molten PHA and separating the layer of PHA optionally after it cooling to form a solid.

Abstract: A method for converting compactin to pravastatin is described. Compactin is provided and contacted with an agent derived from Actinomadura under conditions in which the agent converts compactin to pravastatin. Also described are an Actinomadura strain, an Actinomadura cell free extract, an Actinomadura hydroxylase, and a method for lowering cholesterol levels in mammals.

Abstract: There is disclosed a process for producing D-pantoic acid or D-pantothenic acid utilizing the capability of the microorganism to synthesize D-pantoic acid or D-pantothenic acid. According to this process, (a) D-pantoic acid is biosynthesized from various carbon sources such as glucose to accumulate it in the culture medium, or (b) .beta.-alanine is contacted with the microorganism by, for example, adding .beta.-alanine to the culture medium, to cause condensation of the biosynthesized D-pantoic acid with .beta.-alanine to accumulate D-pantothenic acid in the medium.

Abstract: A process for hydroxylating compounds of the formula ##STR1## where n, A and R.sup.1 to R.sup.4 have the meanings stated in the description, with the aid of microorganisms of the genus Beauveria.

Abstract: Poly(3-hydroxybutanoic acid) having a number average molecular weight of not less than 500,000 is oriented at a draw ratio of 2-fold or more to reproducibly obtain a film made of poly(3-hydroxybutanoic acid) having biodegradability and biocompatibility as well as sufficient strength and flexibility (for example, tensile strength of not less than 30 MPa and elongation to break of not less than 15%).

Abstract: A hydroxyalkanoic acid (PHA)is recovered from matter derived from living organisms by dissolving the PHA in a solvent which is a lower ketone, dialkyl ether or a lower alcohol or a monocarboxylic acid ester thereof, separating the solution from such matter and recovering PHA from the solution.

Abstract: The present invention is an economical fermentation method for the production of carboxylic acids comprising the steps of a) inoculating a medium having a carbon source with a carboxylic acid-producing organism; b) incubating the carboxylic acid-producing organism in an aerobic atmosphere to promote rapid growth of the organism thereby increasing the biomass of the organism; c) controllably releasing oxygen to maintain the aerobic atmosphere; d) controllably feeding the organism having increased biomass with a solution containing the carbon source to maintain the concentration of the carbon source within the medium of about 0.5 g/L up to about 1 g/L; e) depriving the aerobic atmosphere of oxygen to produce an anaerobic atmosphere to cause the organism to undergo anaerobic metabolism; f) controllably feeding the organism having increased biomass a solution containing the carbon source to maintain the concentration of the carbon source within the medium of .gtoreq.

Abstract: Bacillus sp. TTUR 302 which belongs to the genus Bacillus and is capable of converting bile acids having a 7.alpha.-hydroxyl group or a 7-keto group into bile acids having a 7.beta.-hydroxyl group; and a process for producing bile acids having a 7.beta.-hydroxyl group which comprises incubating this microorganism in an enriched medium containing bile acids having a 7.alpha.-hydroxyl group or a 7-keto group and collecting the formed bile acids having a 7.beta.-hydroxyl group (ursodeoxycholic acids, etc.). The process is easy to operate and safe as compared with the conventional chemical synthesis method. It is also superior to the conventional microbial methods particularly in the case of industrial production, since the microorganism of the invention is a facultative anaerobe and thus capable of effecting the conversion of the bile acids under aerobic conditions at a high substrate concentration.

Abstract: Method for the production of vanillic acid and vanillin by bioconversion from ferulic acid in a medium containing phospholipids cultured with at least one microorganism from the classes Ascomycetes, Basidiomycetes or Actinomycetes. Vanillin is also produced by bioconversion of vanillic acid by at least one microorganism of the class Basidiomycetes in a medium containing cellobiose.

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 present invention relates to a process for separating polyhydroxyalkanoate (PHA) from a biomass comprising the PHA, the process comprising: a) treating the biomass with a PHA solvent and a marginal nonsolvent for PHA; b) removing any insoluble biomass, thereby leaving behind a solution of PHA and marginal nonsolvent for PHA; and c) removing the PHA solvent from the solution, thereby resulting in a suspension of precipitated PHA in the marginal nonsolvent for PHA. Optionally, the process further comprises removing the marginal nonsolvent for PHA, thereby leaving behind the PHA. The present invention further relates to the suspension and the PHA produced by the process.

Abstract: A method for producing an L-lactic acid with an optical purity of not lower than 70% comprising the steps of:(a) cultivating a microorganism of the genus Bacillus, in particular, Bacillus cereus and Bacillus thuringiensis, capable of producing an L-lactic acid with an optical purity of not lower than 70% from an assimilable carbon source; and (b) collecting an L-lactic acid with an optical purity of not lower than 70% from the culture.

Abstract: Enzymes with modified substrate specificity and methods of obtaining same by the steps of a) determining the structure of two or more enzymes in the same group, b) comparing the structure of the substrate binding sites of the enzymes, and c) modifying selected amino acids by genetic mutation so that the substrate preference of one of the enzymes is altered. The methods are particularly useful for the stereospecific interconversion of oxyacids and aminoacids.

Abstract: The invention provides a process for producing gamma-lactones useful for incorporation in flavorings and fragrances, wherein a micro-organism which is acceptable for making food grade products and which does not metabolize gamma-lactones, is cultured aerobically in a culture medium containing as the substrate a hydroxy fatty acid having an even number 4 of carbon atoms between the carboxyl group and the carbon atom carrying the hydroxy group. The preferred micro-organism is a Saccharomyces cerevisiae, Debaromyces hansenii or Candida boidinii species. The gamma-hydroxy-alkanoic acid reaction product of the process is lactonized either in the fermentation broth or after separation therefrom. Especially suitable are 12-hydroxy fatty acids such as ricinoleic acid. The hydroxy fatty acid may be added either pure or as the mixture obtained by hydrolysis of an ester thereof. Enzymatic hydrolysis of such ester may be done in situ in the fermentation broth.

Abstract: A process is described for producing organic acids such as lactic acid. The process includes the steps of producing lactic acid by fermentation, resulting in an aqueous fermentation broth containing lactic acid, and adding a calcium base, such as calcium carbonate, to the fermentation broth, thereby producing calcium lactate in the broth. Biomass is removed from the broth, thereby leaving an aqueous solution or dispersion of calcium lactate. The calcium lactate is reacted with a source of ammonium ions, such as ammonium carbonate, or a mixture of ammonia and carbon dioxide, thereby producing an ammonium lactate. Contaminating cations can be removed by ion exchange. The free lactic acid or a derivative thereof can be separated from the ammonium ions, preferably by salt-splitting electrodialysis.

Abstract: A fortified enzyme preparation of the gorgonian Pseudopterogorgia americana has been developed which efficiently transforms a variety of sterols to their 9(11)-secosteroid derivative in high yield. NAD, NADP, and glutamate dehydrogenase are key additives in this enzymatic conversion. In addition to naturally-occurring metabolites, novel secosteroids have been prepared.

Abstract: A process is disclosed for preparing an organic acid and/or its salts from a solution obtained through fermentation. In this process, a pure carbohydrate-containing raw material is used. The acid-containing solution prepared by means of fermentation is supplied to a cell separation, and the acid-containing permeate is supplied to a protein precipitation, where it is mixed with a silicon-containing precipitant at temperatures between 2.degree. and 70.degree. C. The solution thus obtained is supplied to a protein separation, and the acid-containing permeate is concentrated and then supplied to a single- or multi-stage crystallization or a granulation.

Abstract: 2-hydroxyphenylacetic acid is prepared from phenylacetic acid by fermentation with suitable microorganisms.

Abstract: A reaction system, wherein a cyanohydrin is converted into an optically active .alpha.-hydroxy acid or .alpha.-hydroxyamide via a treatment with a microorganism, is provided with an automatic cyanohydrin controller comprising a cyano ion detector, a regulator and a cyanohydrin supplier linked thereto. The reaction is performed while automatically controlling the cyanohydrin concentration.Thus cyanohydrin can be supplied under automatic control at a relatively low and constant concentration on the basis of its consumption ratio. The reaction rate of the catalyst can be continuously regarded as the rate-limiting factor. As a result, a decrease in the enzymatic activity during the reaction can be suppressed and an optically active .alpha.-hydroxy acid or .alpha.-hydroxyamide can be efficiently obtained at a high yield.

Abstract: A biological process for predominantly producing an optically active .alpha.-hydroxycarboxylic acid having a phenyl group directly from a racemic .alpha.-hydroxynitrile or a mixture of an aldehyde corresponding to the nitrile and prussic acid as a substrate is disclosed, comprising reacting a microorganism belonging to the genus Rhodococcus, Alcaligenes, Brevibacterium or Pseudomonas with the substrate in a neutral to basic aqueous medium. A desired optically active .alpha.-hydroxycarboxylic acid having a phenyl group can be obtained quantitatively at a high optical purity.

Abstract: A process for the production of a homochiral 2-hydroxy carboxylic acid or salt thereof corresponding to general formula (I), wherein R represents one of formulae (II), (III), (IV), (V), wherein R' represents straight- or branched-chain alkyl or phenyl optionally para-substituted with methyl, methoxy, nitro or amino; and R" represents hydrogen, halogen or phenyl optionally para-substituted with methyl, methoxy, nitro or amino; and M represents hydrogen or a salt-forming moiety; characterized in that it comprises reducing a corresponding 2-keto carboxylic acid or salt thereof using a (R)- or (S)-2-oxo carboxylic acid dehydrogenase, inter alia, is disclosed.

Abstract: Disclosed is a process for accumulating a poly-3-hydroxy butyric acid in bacterial cells by continuously fermenting a methanol-assimilating bacterium having a capability of producing a poly-3-hydroxy butyric acid, in a single fermentation vessel by using methanol as carbon source at a limited feeding rate of nitrogen, phosphorus, or potassium such that the retention time for the fermentation is more than 10 hours.

Abstract: The invention relates to a novel process for preparing 3-hydroxyphenylacetic acid by cultivating a fungus of the genus Rhizoctonia, Ceratobasidium and Pellicularia in the presence of a phenyl compound of the formula I ##STR1## where X is COOR, CH.sub.2 OH, CH.sub.2 NH.sub.2 or ##STR2## R is methyl, ethyl, hydrogen, sodium, potassium or ammonium.