Abstract: An automated apparatus and method for analyzing liquid samples by forming discrete sample aliquots (boluses) in an elongated conduit which contains a hydrophobic carrier liquid. Aliquots may be analyzed by adding at least one reagent to the sample aliquot that reacts selectively with an analyte contained therein. The reaction product, which is selective for the analyte of interest and proportional to its concentration, is measured with an appropriate detector. Intrinsic sample properties of the sample may also be measured without the need for adding chemical reagents. The invention enables simple and accurate testing of samples using time honored wet-chemical analysis methods in microliter volume regimes while producing remarkably small volumes of waste.

Abstract: The present invention describes a process for the synthesis of a semi-synthetic ?-lactam compound from a nucleus and a side chain selected from the group consisting of D-phenylglycine and D-dihydro-phenylglycine in the form of a side chain ester and an enzyme catalyzing the coupling of the side chain ester to the nucleus characterized in that the side chain ester is not isolated as a solid intermediate.

Abstract: A separation chip for separating an insoluble component from a suspension using centrifugal force by rotation, includes a suspension holding tank, a separation liquid holding tank, and an insoluble component holding tank arranged in order from an inner circumferential side during rotation, wherein the suspension holding tank and the insoluble component holding tank are connected to each other, the insoluble component holding tank and the separation liquid holding tank are connected to each other by a narrow portion, and in the insoluble component holding tank, a connecting portion with the suspension holding tank is positioned further toward an outer circumferential side than the narrow portion.

Abstract: The present invention discloses isolation of Penicillin Acylase (PA) from Achromobacter sp CCM 4824 expressed in recombinant strain E. coli BL21 CCM 7394 bearing the recombinant plasmid pKXIP1 and processing of PA into biocatalyst useful for the industrial synthesis of antibiotics. More particularly the invention discloses a synthesis of semi-synthetic ?-lactam antibiotics in the reaction mixture consisting of activated acyl-donor (D-p-hydroxyphenylglycine methyl ester or amide for Amoxicillin and Cefadroxil; D-phenylglycine methyl ester or amide for Ampicillin and Cephalexin) and nucleophile (6-APA or 7-ADCA) catalyzed by PA obtained from recombinant E. coli BL21 CCM 7394 as the biocatalyst.

Abstract: The promoter region associated with the Yarrowia lipolytica glycerol-3-phosphate O-acyltransferase (gpat) gene has been found to be particularly effective for the expression of heterologous genes in oleaginous yeast. The promoter regions of the instant invention have been shown to be suitable to drive high-level expression of genes involved in the production of ?-3 and ?-6 fatty acids.

Abstract: Provided are a microorganism capable of producing L-threonine and having an inactivated tyrR gene, a method of producing the same and a method of producing L-threonine using the microorganism. The microorganism can be used to produce L-threonine in high yield.

Abstract: Nucleotide sequences encoding formate dehydrogenases D & E and a method for preparing succinic acid using the same, more particularly, formate dehydrogenases D & E converting formate to carbon dioxide and hydrogen, fdhD and fdhE nucleotide sequences encoding the formate dehydrogenases D & E, recombinant vectors containing the nucleotide sequences, microorganisms transformed with the recombinant vectors, and a method for preparing succinic acid using the transformed microorganism.

Abstract: Provided are a microorganism capable of producing L-threonine and having an inactivated galR gene, a method of producing the same and a method of producing L-threonine using the microorganism. The microorganism can be used to produce L-threonine in high yield.

Abstract: The invention relates to a mutant strain of bacteria, which either lacks or contains mutant genes for several key metabolic enzymes, and which produces high amounts of succinic acid under anaerobic conditions.

Abstract: Transacylase enzymes and the use of such enzymes to produce paclitaxel, related taxoids, as well as intermediates in the paclitaxel biosynthetic pathway are disclosed. Also disclosed are nucleic acid sequences encoding the transacylase enzymes.

Abstract: The thin film transistor has a non-transparent structure besides and insulated with the gate. Hence, the light transmitted from the substrate is blocked and the light current induced in the thin film transistor is negligible. The method uses a mask with a slit pattern to form a non-uniform photoresist. Hence, the mask could be used to pattern two conductor layers for forming source/drain/channel.

Abstract: The present invention discloses a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.

Abstract: The invention relates to a process for the preparation of an antibiotic, in particular cefalexin, ampicillin, amoxicillin, cefaclor, cefradin, cefadroxil, cefotaxim and the like, wherein a beta-lactam core is acylated, the antibiotic is recovered from the reaction mixture, the remaining mother liquor is subjected to a hydrolysis reaction in which the antibiotic present in the mother liquor is decomposed into its initial compounds, in particular the beta-lactam core, and the acylation agent is hydrolized. The beta-lactam core can then be recovered virtually quantitatively or recycled to the acylation reaction. This is because it has been found that the solubility of the beta-lactam core is unexpectedly high at relatively high concentrations of acylation agent and antibiotic.

Abstract: Metabolic engineering is used to increase the carbon flow toward oxaloacetate to enhance production of bulk biochemicals, such as lysine and succinate, in bacterial fermentations. Carbon flow is redirected by genetically engineering the cells to overexpress the enzyme pyruvate carboxylase.

Abstract: A liquid chemical stripping or cleaning solution is selected by combinatorial high throughput screening. A high throughput screening well array assembly includes (A) a metal substrate and (B) a mask that defines an array of wells on the substrate. A combinatorial high throughput screening system includes (A) a metal substrate and (B) a mask that defines an array of wells on the substrate and a reaction vessel to receive the well array assembly.

Abstract: New mutant penicillin G acylases preferably from E. coli are provided, exhibiting altered enzymatic activity. These penicillin G acylases are obtained by expression of a gene encoding said penicillin G acylase having an amino acid sequence which differs at least in one amino acid from the wild-type penicillin G acylase.

Abstract: The invention relates to a method for preparing a &bgr;-lactam antibiotic, wherein an N-substituted &bgr;-lactam, having general formula (I), wherein R0 is hydrogen or C1-3 alkoxy; Y is CH2, oxygen, sulfur, or an oxidized form of sulfur; Z is (a), (b), (c) or (d), wherein R1 is hydrogen, hydroxy, halogen, C1-3 alkoxy, optionally substituted, optionally containing one or more heteroatoms, saturated or unsaturated, branched or straight C1-5 alkyl, preferably methyl, optionally substituted, optionally containing one or more heteroatoms C5-8 cycloalkyl, optionally substituted aryl or heteroaryl, or optionally substituted benzyl; and X is (CH2)m-A-(CH2)n, wherein m and n are the same or different and are chosen from the group of integers 0, 1, 2, 3 or 4 and A is CH═CH, C═C, CHB, C═O, optionally substituted nitrogen, oxygen, sulfur or an optionally oxidized form of sulfur, and B is hydrogen, halogen, hydroxy, C1-3 alkoxy, or optionally substituted methyl, or a salt thereof, is contacted with at least

Abstract: Beta-lactam antibiotics are synthesized by reacting an amino-beta-lactam component with a corresponding amino-group-containing acylating side-chain component in the presence of penicillin amidase from E. coli covalently immobilized on support particles. The resulting beta-lactam antibiotic product is solubilized by adding an acid such as sulfuric acid to lower the pH to 1.0 at a temperature in the range of 0° C. to +5° C. The immobilized penicillin amidase is substantially inactivated by the acid. After separating the beta-lactam antibiotic product, the immobilized penicillin amidase is substantially reactivated for reuse in antibiotic synthesis by treatment with a buffer having about a neutral pH. Antibiotics that can be produced include ampicillin, amoxicillin, cephalexin, cefaclor and cefadroxil.

Abstract: Penicillin G acylase is immobilized by covalent bonding to a crosslinked mixture of a gelled gelling agent such as gelatin and a polymer containing free amino groups such as alginate amine, chitosan or polyethylene imine. The immobilized penicillin G acylase provides a higher synthesis/hydrolysis ratio as compared to immobilizing with other carriers when producing .beta.-lactam derivatives by a condensing reaction of an amino .beta.-lactam with an acylating agent. The acylating agent may be a derivative of D-phenylglycine, a derivative of D-p-hydroxyphenylglycine or a derivative of D-2,5-dihydro-phenylglycine. Examples of .beta.-lactam derivatives that can be produced are amoxycillin, ampicillin, cephaclor, cephadroxil, cephprozil, cephalexin and cephradine.

Abstract: An improvement for enzymatically syhnthesizing a .beta.-lactam compound is presented. The improvement comprises catalyzing the acylation of an amino .beta.-lactam with an acylating agent for at least 5 hours with an amidase or acylase, wherein the concentration of each reactant is constantly higher than 70% of the lowest value of the saturated concentration of both reactants.

Abstract: New mutant .beta.-lactam Penicillin G acylases are provided, exhibiting altered substrate specificities. These Penicillin G acylases are obtained by expression of a gene encoding said Penicillin G acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type Penicillin G acylase.

Abstract: A semi-quantitative method for determining the concentration of viable coliforms or E. coli in a liquid is provided. The sample to be tested is mixed with an indicator reagent which includes a specific indicator compound that undergoes a change that is detectable by spectrophotometric or visual methods upon cleavage by a beta galactosidase enzyme found in coliforms or a beta glucuronidase enzyme unique to E. coli.

Abstract: Process for the recovery of ampicillin from a mixture containing ampicillin and 6-aminopenicillic acid (6-APA), in which a mixture of ampicillin and 6-APA, with a pH higher than 7, which apart from any solid ampicillin being present is homogeneous at a pH between 7 and 8.5, is subjected to a pH lowering till a pH lower than 8.2 is reached, and the solid substance present is recovered. The process is in particular suitable to be applied to the reaction mixture which is obtained after the enzymatic acylation reaction of 6-APA with a phenylglycidine derivative as acylation agent. Pure ampicillin can thus be recovered in a simple way.

Abstract: New mutant .beta.-lactam Penicillin G acylases are provided, exhibiting altered substrate specificities. These Penicillin G acylases are obtained by expression of a gene encoding for said Penicillin G acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type Penicillin G acylase.

Abstract: An enzyme selected from penicillin-G amidase, glutaryl-7-ACA acylase and D-amino acid oxidase is immobilized by covalent bonding on an aminofunctional organosiloxane polymer carrier to provide an immobilized enzyme having a specific volume activity of at least 100 U/g wet carrier. Preferably, the carrier has an average diameter or 0.01 to 3 mm and is essentially spherical. Covalent bonding is accomplished by activating amino groups on the carrier with a dialdehyde and reacting the activated groups with reactive groups on the enzyme. An amount of enzyme is immobilized to provide a weight ratio of enzyme to carrier of 1 to 300 mg protein per g wet carrier.

Abstract: A method for providing a semisynthetic .beta.-lactam antibiotic by enzyme catalyzed acylation of the parent .beta.-lactam with an activated derivative of the side chain acid wherein a modulator, which consists of one or more compounds different from the reactants and the reaction product and which suppresses the hydrolysis of the activated derivative of the side chain acid and the desired product more than it suppresses the synthesis of the desired product, is added to the reaction mixture, at the beginning of the reaction process, in a concentration from about 0.2 to 100.times.10.sup.3 .mu.m.

Abstract: .beta.-Lactam derivatives are synthesized by an enzymatic reaction of the parent amino .beta.-lactam with the corresponding acylating agent, the concentration of the acylating agent plus the concentration of .beta.-lactam derivative in the reaction mixture being above about 400 mM.

Abstract: New mutant .beta.-lactam acylases are provided exhibiting altered substrate specificities. These .beta.-lactam acylases are obtained by expression of a gene encoding said .beta.-lactam acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type .beta.-lactam acylase.

Abstract: Synthesis of semi-synthetic monobactamic or .beta.-Lactamic antibiotics by using derivatives stabilized by various methods of penicillin G acylase from various microbial sources according to a thermodynamically controlled strategy in monophase water/cosolvent organic apolar systems, wherein the concentration of the cosolvent varies between 30% and 90%, the temperature between -10.degree. C. and 50.degree. C., the pH between 4.5 and 8.5, with concentrations of the antibiotic nucleus between 0.5 an 875 mM and acyl donor between 0.2 mM and 1M, with a relationship antibiotic ring/activated or free acyl donor, using a buffer between 0 and 1M. Application to the pharmaceutical industry.

Abstract: A process for preparing a compound of formula I: ##STR1## wherein R.sub.1 represents a hydroxy protecting group and R.sub.2 represents a carboxy protecting group, which comprises:hydrolyzing a compound of formula II ##STR2## wherein R.sub.1 and R.sub.2 are as defined above and R represents an alkyl, alkenyl or phenylalkyl group having from 1 to 18 carbon atoms, in the presence of an enzyme capable of selectively hydrolyzing the ester group of the 2-substituent thereof.

Abstract: The operating latitude of the tri-level xerographic process is improved by replacing the standard DC bias that is applied to one or both of the developer housings in conventional tri-level imaging with a chopped DC (CDC) developer bias. Chopped DC biasing is the alternate application of two discrete bias voltages to a developer stucture in a periodic fashion at a given frequency, with the period of each cycle divided up between the two bias levels at a duty cycle of from 5%-10% or 90%-95% depending upon which of the two developer structures is being biased. In the case of the DAD developer structure the duty cycle of higher of the two biases is 5%-10% and in case of a CAD developer structure the duty cycle of higher of the two biases is 90%-95%.

Abstract: The present invention relates to a new method of protection of the carboxy group in the chemistry of the compounds of .beta.-lactam type. According to such a method, the carboxy group is protected by being transformed into its corresponding phenyl-acetoxy-methyl ester, which is then removed by an enzymatic route by means of penicillinacylase.In particular, if the .beta.-lactam compound also bears a phenyl-acetamidic substitutent, this latter is simultaneously hydrolysed during the same step of removal of the carboxy function protecting group.

Abstract: Process for producing S-adenosyl-L-homocysteine, which comprises reacting adenosine with homocysteine by contacting them in an aqueous medium in the presence of cells or treated cells of a microorganism of a specified genus having the ability to synthesize S-adenosyl-L-homocysteine from adenosine and homocysteine, and collecting the S-adenosyl-L-homocysteine synthesized.

Abstract: A method for the formation of intramolecular amide bonds by the action of cyanogen, under mild reaction conditions, in the preparation of cyclic amides, including lactams, in biologically active compounds. A compound containing at least one carboxylic acid group and at least one primary or secondary amino group is reacted with cyanogen to form an intramolecular amide bond. The method has utility in the synthesis of B-lactam antibiotics, such as penicillins, cephalosporins, and their derivatives, in enzyme modification, in cyclization of peptides, and in covalent cross-linking of proteins.

Abstract: Penicillins and cephalosporins can be synthesized by the action of an acylase on a penicillin or cephalosporin nucleus amine as substrate and an ester (I) of the following formula as the acyl source: ##STR1## (wherein RCO is an acyl group in penicillin or cephalosporin side chains;X is a hydrogen atom, lower alkyl group or hydroxy-lower alkyl group;Y is a hydrogen atom or a lower alkyl group; and n is a positive integer).The novel acyl source (I) is also disclosed.

Abstract: Penicillin V is prepared by culturing a penicillin-producing microorganism in a medium containing suitable sources of nitrogen, carbon and energy, and inorganic salts. One or more phenoxyalkanes of the formula ##STR1## wherein n is an integer from 6 to 13 are included within the medium as the sidechain precursor.

Abstract: A water-soluble non-colloidal penicillinacylase preparation containing penicillinacylase covalently bound to a water-soluble carrier is produced by reacting penicillinacylase with an activated derivative of a water soluble polysaccharide in aqueous solution. The water-soluble penicillinacylase preparation efficiently hydrolyzes penicillin and permits recovery of 6-aminopenicillanic acid efficiently in extremely high purity.