Abstract: A method of identifying an antifungal agent which targets a PPTB protein of a fungus comprising determining whether a candidate compound binds to or inhibits a PPTB protein, wherein binding or inhibition indicates that the candidate substance is an antifungal agent.

Abstract: A mutant hydroxylase with increased activity and greater substrate specificity towards phenylacetyl-7-ADCA derivatives for the production of phenylacetyl-7-HACA derivatives, which carries one or more amino acid modification at residue positions when compared with certain wild type hydroxylase from certain groups of residues. Also disclosed is a process for the preparation of deacetyl cephalosporanic acid from the corresponding deacetoxy cephalosporanic acid that includes an enzyme of the present invention. Also provided is a method for the production and processing of such enzymes.

Abstract: The present invention relates to a crystalline form of an intermediate for cefoperazone of formula (1) and to a process for the preparation thereof by enzymatic condensation of a 3?-thiosubstituted ?-lactam nucleus with a phenylglycine derivative.

Abstract: The present invention relates to the use of nucleic acid molecules coding for a bacterial xylose isomerase (XI), preferably coming from Clostridium phytofermentans, for reaction/metabolization, particularly fermentation, of recombinant microorganisms of biomaterial containing xylose, and particularly for the production of bioalcohols, particularly bioethanol, by means of xylose fermenting yeasts. The present invention further relates to cells, particularly eukaryotic cells, which are transformed utilizing a nucleic acid expression construct which codes for a xylose isomerase, wherein the expression of the nucleic acid expression construct imparts to the cells the capability to directly isomerize xylose into xylulose. Said cells are preferably utilized for reaction/metabolization, particularly fermentation, of biomaterial containing xylose, and particularly for the production of bioalcohols, particularly bioethanol.

Abstract: The present invention relates to the use of nucleic acid molecules coding for a bacterial xylose isomerase (XI), preferably coming from Clostridium phytofermentans, for reaction/metabolization, particularly fermentation, of recombinant microorganisms of biomaterial containing xylose, and particularly for the production of bioalcohols, particularly bioethanol, by means of xylose fermenting yeasts. The present invention further relates to cells, particularly eukaryotic cells, which are transformed utilizing a nucleic acid expression construct which codes for a xylose isomerase, wherein the expression of the nucleic acid expression construct imparts to the cells the capability to directly isomerize xylose into xylulose. Said cells are preferably utilized for reaction/metabolization, particularly fermentation, of biomaterial containing xylose, and particularly for the production of bioalcohols, particularly bioethanol.

Abstract: The present invention relates to host cells transformed with a nucleic acid sequence encoding a eukaryotic xylose isomerase obtainable from an anaerobic fungus. When expressed, the sequence encoding the xylose isomerase confers to the host cell the ability to convert xylose to xylulose which may be further metabolized by the host cell. Thus, the host cell is capable of growth on xylose as carbon source. The host cell preferably is a eukaryotic microorganism such as a yeast or a filamentous fungus. The invention further relates to processes for the production of fermentation products such as ethanol, in which a host cell of the invention uses xylose for growth and for the production of the fermentation product. The invention further relates to nucleic acid sequences encoding eukaryotic xylose isomerases and xylulose kinases as obtainable from anaerobic fungi.

Abstract: Scalable biomaterial-based bioreactors are described. In one embodiment, the bioreactor may comprise perforated plates stacked such that the assembled bioreactor has the necessary manifolds and chambers to transport gas and liquids to a biomaterial contained within the bioreactor, and to remove the reaction products. In another embodiment, single use bioreactors are described. Methods of operating the bioreactors are also described.

Abstract: The present invention relates to genetic modifications in eukaryotic host cells that have been transformed to express a xylose isomerase that confers on the host cell the ability to isomerize xylose to xylulose. These genetic modifications are aimed at improving the efficiency of xylose metabolism and include, e.g., reduction of nonspecific aldose reductase activity, increased xylulose kinase activity and increased flux of the pentose phosphate pathway. The modified host cells of the invention are suitable for the production of a wide variety of fermentation products, including ethanol, in fermentation processes in which a source of xylose or a source of xylose and glucose are used as carbon source.

Abstract: This disclosure relates to novel xylose isomerases and their uses, particularly in fermentation processes that employ xylose-containing media.

Abstract: The invention relates to a cell which comprises a nucleotide sequence encoding a xylose isomerase, wherein the amino acid sequence of the xylose isomerase has at least 75% sequence identity to the amino acid sequence set out in SEQ ID NO: 2 and wherein the nucleotide sequence is heterologous to the host. A cell of the invention may be used in a process for producing a fermentation product, such as ethanol. Such a process may comprise fermenting a medium containing a source of xylose with a cell of the invention such that the cell ferments xylose to the fermentation product.

Abstract: Bioreactors, and particularly, photobioreactors having a reactor chamber and surge driver, and methods for using these devices, for example, for the production of carbon-based products are provided. The reactor chamber provides a housing for microorganisms and culture medium. The surge driver produces a surge of the microorganisms and/or culture medium in the reactor chamber.

Abstract: Disclosed are methods useful in multiplex cell-based assays for compound screening employing imaging instrumentation. The methods described herein offer high content information relating to the biological potency of test agents, off-target effects and cellular toxicity of potential drug candidates.

Abstract: Polypeptides were identified among translated coding sequences from a metagenomic cow rumen database, that were shown to provide xylose isomerase activity in yeast cells. The xylose isomerase activity can complete a xylose utilization pathway so that yeast can use xylose in fermentation, such as xylose in biomass hydrolysate.

Abstract: A novel xylose isomerase nucleotide sequence obtained from a bovine rumen fluid metagenomic library and also provides the amino acid sequence encoded by the nucleotide sequence, and a vector and a transformant containing the nucleotide sequence. When the xylose isomerase is expressed, a host cell is endowed with the capability of converting xylose into xylulose, and the xylulose is further metabolized by the host cell. Therefore, the host cell can take the xylose as a carbon source for growth. The xylose isomerase from a new source is expressed with high activity in Saccharomyces cerevisiae and is a mesophilic enzyme with optimal temperature of 60° C.

Abstract: The present invention relates to a cell suitable for production of one or more fermentation product from a sugar composition comprising glucose, galactose, arabinose and xylose, wherein the cell comprises two to fifteen copies of one or more xylose isomerase gene or two to fifteen copies of one or more xylose reductase and xylitol dehydrogenase, and two to ten copies of araA, araB and araD, genes, wherein these genes are integrated into the cell genome.

Abstract: The invention relates to a process for the production of cells which are capable of converting arabinose, comprising the following steps: a) Introducing into a host strain that cannot convert arabinose, the genes AraA, araB and araD, this cell is designated as constructed cell; b) Subjecting the constructed cell to adaptive evolution until a cell that converts arabinose is obtained, c) Optionally, subjecting the first arabinose converting cell to adaptive evolution to improve the arabinose conversion; the cell produced in step b) or c) is designated as first arabinose converting cell; d) Analysing the full genome or part of the genome of the first arabinose converting cell and that of the constructed cell; e) Identifying single nucleotide polymorphisms (SNP's) in the first arabinose converting cell; and f) Using the information of the SNP's in rational design of a cell capable of converting arabinose; g) Construction of the cell capable of converting arabinose designed in step f).

Abstract: A novel xylose isomerase nucleotide sequence obtained from a bovine rumen fluid metagenomic library and also provides the amino acid sequence encoded by the nucleotide sequence, and a vector and a transformant containing the nucleotide sequence. When the xylose isomerase is expressed, a host cell is endowed with the capability of converting xylose into xylulose, and the xylulose is further metabolized by the host cell. Therefore, the host cell can take the xylose as a carbon source for growth. The xylose isomerase from a new source is expressed with high activity in Saccharomyces cerevisiae and is a mesophilic enzyme with optimal temperature of 60° C.

Abstract: The present invention relates to genetic modifications in eukaryotic host cells that have been transformed to express a xylose isomerase that confers on the host cell the ability to isomerize xylose to xylulose. These genetic modifications are aimed at improving the efficiency of xylose metabolism and include. e.g., reduction of nonspecific aldose reductase activity, increased xylulose kinase activity and increased flux of the pentose phosphate pathway. The modified host cells of the invention are suitable for the production of a wide variety of fermentation products, including ethanol, in fermentation processes in which a source of xylose or a source of xylose and glucose are used as carbon source.

Abstract: The invention relates to an eukaryotic cell expressing nucleotide sequences encoding the ara A, ara B and ara D enzymes whereby the expression of these nucleotide sequences confers on the cell the ability to use L-arabinose and/or convert L-arabinose into L-ribulose, and/or xylulose 5-phosphate and/or into a desired fermentation product such as ethanol. Optionally, the eukaryotic cell is also able to convert xylose into ethanol.

Abstract: The invention relates to a process for the preparation of a fermentation product from ligno-cellulosic material, comprising the following steps: a) optionally pre-treatment b) optionally washing; c) enzymatic hydrolysis; d) fermentation; and e) optionally recovery of a fermentation product; wherein in step c) an enzyme composition is used that has a temperature optimum of 55 degrees C. or more, the hydrolysis time is 40 hours or more and the temperature is 50 degrees C. or more.

Abstract: The present invention relates to a process for the production of one or more fermentation product from a sugar composition, comprising the following steps: a) fermentation of the sugar composition in the presence of a yeast belonging to the genera Saccharomyces, Kluyveromyces, Candida, Pichia, Schizosaccharomyces, Hansenula, Kloeckera, Schwanniomyces or Yarrowia, and b) recovery of the fermentation product, wherein the yeast comprises the genes araA, araB and araD and the sugar composition comprises glucose, galactose and arabinose.

Abstract: The invention relates to a cell which comprises a nucleotide sequence encoding a xylose isomerase, wherein the amino acid sequence of the xylose isomerase has at least about 70% sequence identity to the amino acid sequence set out in SEQ ID NO: 3 and wherein the nucleotide sequence is heterologous to the host. A cell of the invention may be used in a process for producing a fermentation product, such as ethanol. Such a process may comprise fermenting a medium containing a source of xylose with a cell of the invention such that the cell ferments xylose to the fermentation product.

Abstract: The present invention relates to a process for the synthesis of cefaclor, which process comprises reacting 7-amino-3-chloro cephalosporanic acid (7-ACCA) with D-phenylglycine in activated form (PGa) in the presence of an enzyme in a reaction mixture to form cefaclor, wherein at least part of 7-ACCA and/or PGa are added to the reaction mixture during the course of the reaction. The invention also relates to an aqueous mixture comprising an amount of cefaclor of >10 (w/w) %, an amount of 7-amino-3-chloro cephalosporanic acid of <2 (w/w) %, and an amount of D-phenyl glycine of <2 (w/w) % and a process for the recovery of cefaclor from this aqueous mixture. The invention also relates to cefaclor in crystal form having an absorbance at 400 nm (A400) of less than 0.250.

Abstract: The invention relates to a method for preparing 7-methoxy-3-desacetylcefalotin by a hydrolysis process which takes place in water and is catalyzed by an enzyme obtained from Bacillus pumulis possessing acetyl hydrolasic activity.

Abstract: The present invention relates to the use of nucleic acid molecules coding for a bacterial xylose isomerase (XI), preferably coming from Clostridium phytofermentans, for reaction/metabolization, particularly fermentation, of recombinant microorganisms of biomaterial containing xylose, and particularly for the production of bioalcohols, particularly bioethanol, by means of xylose fermenting yeasts. The present invention further relates to cells, particularly eukaryotic cells, which are transformed utilizing a nucleic acid expression construct which codes for a xylose isomerase, wherein the expression of the nucleic acid expression construct imparts to the cells the capability to directly isomerize xylose into xylulose. Said cells are preferably utilized for reaction/metabolization, particularly fermentation, of biomaterial containing xylose, and particularly for the production of bioalcohols, particularly bioethanol.

Abstract: The present invention relates to a mutant prokaryotic penicillin G acylase derived from a wild-type penicillin G acylase characterized in that the mutant is having an amino acid substitution at one or more amino acid positions selected from the group consisting of amino acid positions A3, A77, A90, A144 A192, B24, B109, B148, B313, B460 and B488 according to the amino acid numbering of the Escherichia coli penicillin G acylase having the amino acid sequence depicted in SEQ ID No: 1.

Abstract: The invention relates to a cell which comprises a nucleotide sequence encoding a xylose isomerase, wherein the amino acid sequence of the xylose isomerase has at least about 70% sequence identity to the amino acid sequence set out in SEQ ID NO: 3 and wherein the nucleotide sequence is heterologous to the host. A cell of the invention may be used in a process for producing a fermentation product, such as ethanol. Such a process may comprise fermenting a medium containing a source of xylose with a cell of the invention such that the cell ferments xylose to the fermentation product.

Abstract: A method for the modification of a material comprising a non-starch carbohydrate, which method comprises contacting said material comprising a non-starch carbohydrate with a polypeptide which has peroxidase activity and which is: a. a polypeptide comprising an amino acid sequence having at least 55% homology with an amino acid sequence set out in any one of: amino acids 21 to 513 of SEQ NO: 2; amino acids 20 to 510 of SEQ ID NO: 4; amino acids 1 to 493 of SEQ ID NO 6; or amino acids 1 to 491 of SEQ ID NO: 8 or b. a polypeptide encoded by a polynucleotide comprising the nucleotide sequence having at least 55% homology with a nucleotide sequence set out in any one of: nucleotides 61 to 1539 of SEQ ID NO: 1; nucleotides 58 to 1530 of SEQ ID NO: 3; nucleotides 1 to 1479 of SEQ ID NO: 5; or nucleotides 1 to 1473 of SEQ ID NO: 7.

Abstract: The invention provides a membrane comprising a gel reinforced by a support. The membrane has opposing surfaces and a thickness between said surfaces. The gel communicates between the opposing surfaces and allows diffusion of a nutrient solution through the membrane. A bioreactor is also provided, comprising a membrane-supporting structure, and a membrane according to the invention supported on the membrane-supporting structure.

Abstract: The present invention relates to a method for selecting a strain of an organism capable of improved consumption of a mixed substrate comprising two or more carbon sources as compared to a reference strain of the organism, which method comprises: growing a population of the reference strain of the organism in the presence of the two or more carbon sources, wherein the number of generations of growth of the said population on each of the said carbon sources is at least about 50% of the number of generations of growth on the carbon source most preferred by the organism; and selecting the resulting strain of the organism, thereby to select a strain of the organism capable of improved consumption of a mixed substrate comprising the two or more carbon sources as compared to the reference strain of the organism. The invention also relates to strains of organisms selected using such a method.

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: The invention relates to novel antimicrobial agents that are based on ?-lactam derivatives and are produced by reacting previously known ?-lactam derivatives with polyphenol oxidase substrates under the influence of free radicals and by forming salts of any ?-lactam derivatives with polyhexamethylene biguanide hydrogen carbonate. Said novel compounds are suitable as an antibiotic.

Abstract: The present invention discloses a two-step enzyme method for preparing 7-aminocephalosporanic acid from cephalosporin C, wherein D-amino acid oxidase used is purified D-amino acid oxidase mutant of yeast Trigonopsis variabilis, having a specific activity of 105% higher than that of parent D-amino acid oxidase. The method has no need of addition of hydrogen peroxide, ?-lactamase inhibitor, catalase inhibitor, catalase and the like commonly used in the prior art. The productivity of the method can reach more than 93%. Thus, the method is simple, low in cost and high in productivity.

Abstract: The invention relates to an eukaryotic cell expressing nucleotide sequences encoding the ara A, ara B and ara D enzymes whereby the expression of these nucleotide sequences confers on the cell the ability to use L-arabinose and/or convert L-arabinose into L-ribulose, and/or xylulose 5-phosphate and/or into a desired fermentation product such as ethanol. Optionally, the eukaryotic cell is also able to convert xylose into ethanol.

Abstract: The purpose of the present invention is to provide a process for protection of enzymatic biocatalysts, constituted by a primary support, wrapped by a secondary matrix. More particularly, the invention is embodied as a bioreactor with a configuration that preserves the physical integrity and catalytic activity of the biocatalyst after long runs, and at the same time allows an easy separation of the protected biocatalyst from the solid, precipitated during the reaction course. Still more particularly, the invention refers to the use of the bioreactor herein described for the enzymatic synthesis of ?-lactam antibiotics, including the insoluble enzymatic catalysts, which have a primary matrix for immobilization involved by a secondary matrix, which is able to preserve 100% of the catalyst physical integrity and approximately 100% of its catalytic activity.

Abstract: The present invention describes a process for the production of an N-?-amino-hydroxyphenylacetyl or an N-?-aminophenylacetyl ?-lactam antibiotic comprising an IPNS-catalysed conversion of a precursor tripeptide hydroxyphenylglycyl-cysteinyl-valine (HpgCV) or phenylglycyl-cysteinyl-valine (PgCV), respectively, to the N-hydroxyphenylglycyl or the N-phenylglycyl ?-lactam antibiotic, respectively. The tripeptide HpgCV or the tripeptide PgCV may further be prepared by contacting the amino acids hydroxyphenylglycine (Hpg) or phenylglycine (Pg), cystein (C) and valine (V) with a non-ribosomal peptide synthetase (NRPS) to effect formation of the tripeptide HpgCV or the tripeptide PgCV, the NRPS comprising a first module M1 specific for Hpg or Pg, a second module M2 specific for C and a third module M3 specific for V An IPNS is further provided having an improved activity in this conversion, as well as an NRPS catalysing the formation of the tripeptides.

Abstract: The present invention relates to the production of optically active amines, which can be used as intermediate products in a synthesis of for instance pharmaceutical products.

Abstract: The present invention relates to fungal host cells that are transformed with a nucleic acid construct encoding a fungal oxygen-binding proteins or fragments thereof that comprise the oxygen-binding domain. Upon transformation of the host cell with the construct, the oxygen-binding protein confers to the host cell improved fermentation characteristics as compared to untransformed host cells. These characteristics include e.g. increases in oxygen uptake rates, biomass densities, volumetric productivities and/or product yields. The invention further relates to fermentation processes in which the host cells are used and to fungal oxygen binding proteins, in particular fungal flavohemoglobins and hemoglobin domains, and to nucleotides sequences encoding these proteins.

Abstract: Enzymes with cephalosporin C acylase activity obtained by site-directed, random or “site-saturation” mutagenesis of a native sequence optimised for expression in E. coli.

Abstract: The invention relates to a process for the preparation of cephalexin with the aid of a penicillin amidase immobilized on a crosslinked hydrophilic copolymer which has binding activity for ligands having nucleophilic groups and is in bead form.

Abstract: The present invention provides a method for producing a novel ?-lactam antibiotic from a protoplast fusion strain. The method is to fermentatively culture the protoplast fusion strain of Penicillium chrysogenum and Cephalosporium acremonium. The ferment filtrate is isolated, lyophilized, and extracted by acetone or acetone/methanol. The extract is concentrated by decompression, and then analyzed by preparation type HPLC to isolate the active antibiotic compound.

Abstract: Methods for improving the production of a secondary metabolite by a fungus by increasing the yield or productivity of the secondary metabolite produced by the fungus are described. The methods include increasing the expression of LYS14, for example, by transforming a cell with a nucleic acid molecule encoding LYS14.

Abstract: The subject of the present invention is to provide a ?-lactam acylase protein having high activity, a gene coding for said ?-lactam acylase protein, a recombinant vector having said gene, a transformant containing said recombinant vector, and a method of producing a ?-lactam antibiotic such as amoxycillin using said ?-lactam acylase. A ?-lactam acylase gene of Stenotrophomonas maltophilia was cloned, the DNA base sequence and the amino acid sequence expected therefrom was determined, and a Stenotrophomonas ?-lactam acylase gene was obtained. This gene was found to code for a protein with a molecular weight of about 70 kDa and having ?-lactam acylase activity, and could efficiently produce amoxycillin without being inhibited by phenylacetic acid, etc. Furthermore, by modification of the amino acid sequence, a protein which can more efficiently produce amoxycillin could be obtained.

Abstract: A mutated expandase enzyme having higher activity on penicillin G is provided to produce phenylacetyl-7-aminodeacetoxycephalosporanic acid (7-ADCA), which mutated expandase enzyme has one or more amino acid substitutions selected form M73T, S79E, V275I, L277K, C281Y, G300V, N304K, I305L and I305M.

Abstract: An isolated DNA sequence that encodes a peptide with CPC-acetylhydrolase enzymatic activity is disclosed. Also, a method of expressing CPC-acetylhydrolase activity that includes the steps of (a) providing a microorganism that is susceptible to transformation with the isolated DNA sequence and that, upon transformation, expresses the CPC-acetylhydrolase activity encoded by the sequence, and (b) transforming the microorganism with the DNA sequence to cause expression of the CPC-acetylhydrolase activity in the microorganism is disclosed. Also, a method for producing a microorganism with increased capacity to aid in the production of cephalosporin, which method includes the steps of (a) providing a microorganism that has CPC-AH activity by virtue of expression of the DNA sequence or of a fragment thereof coding for the CPC-acetylhydrolase enzyme activity; and (b) inactivating the activity by disrupting expression of the DNA sequence is disclosed.

Abstract: A process for preparing cephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C compound of formula III:— 1

Abstract: A process for preparing cephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C compound of formula III:— 1

Abstract: A mutated expandase enzyme having higher activity on penicillin G is provided to produce phenylacetyl-7-aminodeacetoxycephalosporanic acid (7-ADCA), which mutated expandase enzyme has one or more amino acid substitutions selected form M73T, S79E, V275I, L277K, C281Y, G300V, N304K, I305L and I305M.

Abstract: A process for preparing cephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C compound of formula III: into a 3-thiolated-&agr;-ketoadipyl-7-aminocephalosporanic acid derivative of formula IV: wherein R is a heterocyclic group comprising at least a nitrogen atom. Compounds of formula IV are used in the preparation of cephalosporin C antibiotics and derivatives thereof.

Abstract: A mutated expandase enzyme having higher activity on penicillin G is provided to produce phenylacetyl-7-aminodeacetoxycephalosporanic acid (7-ADCA), which mutated expandase enzyme has one or more amino acid substitutions selected form M73T, S79E, V2751, L277K, C281Y,