Abstract: &bgr;-keto esters are prepared by way of a lipase-catalyzed transesterification. The synthetic methodology provides a simple scheme for the synthesis of optically active &bgr;-keto esters that are useful building blocks and starting materials for natural product synthesis. Moreover, the methodology employs mild, solvent-free conditions. The methodology may also be employed for resolving racemic alcohols.

Abstract: The invention pertains to isolated phosphopantetheinyl transferases, such as the E. coli acyl carrier protein synthase, which transfer a phosphopantetheinyl group onto a substrate. The enzyme can be purified from a natural source, produced recombinantly, or synthetically. Accordingly, the invention provides compositions and kits including phosphopantetheinyl transferases and host cells expressing phosphopantetheinyl transferases. The invention also provides nucleic acids encoding phosphopantetheinyl transferases and vectors comprising such nucleic acids. The invention further provides methods for phosphopantetheinylating a substrate in vitro or in vivo and methods for producing antibiotics in vitro or in vivo.

Abstract: Disclosed is a process for the synthesis of &bgr;-lactam antibacterials using soluble side chain esters in the presence of enzyme acylase. Also disclosed are novel esters useful as reactants in said process.

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: The present invention relates to a modified enzyme of a non-heme iron (II) dependent family of oxygenases and oxidases which renders the enzyme dependent on bicarbonate for activity. In a preferred embodiment, the modification is an arginine, lysine, or other amino acid that is two amino acid residues upstream of a histidine residue that is an iron ligand in the enzyme and is one of the histidine residues of the 2-histidine-1-aspartic acid trifacial motif. In particular, the modified enzymes are isopenicillin N synthetase, deacetoxycephalosporin C synthetase, and deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase which are used to make antibiotics. The present invention further provides a method for making antibiotics using a modified enzyme such as isopenicillin N synthetase, deacetoxycephalosporin C synthetase, and deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase wherein the modification renders the enzyme dependent on bicarbonate for activity.

Abstract: The invention relates to the production of secondary metabolites by fungi. More particularly, the invention relates to improvement of production of commercially important secondary metabolites by fungi. The invention provides methods for improving secondary metabolite production in a fungus, comprising modulating the expression of a gene involved in regulation of secondary metabolite production.

Abstract: A method for the production of clavulanic acid by the fermentation of a clavulanic acid producing microorganism at a controlled level of at least 50 mg/l ammonia has been provided for.

Abstract: The present invention discloses an improved process for the preparation of 6-amino penicillanic acid (6-APA) from a fermentatively produced N-substituted penicillin comprising the steps of extraction of the N-substituted penicillin compound as present in a fermentation broth or fluid to an organic solvent, back extraction of the N-substituted penicillin compound to water, treatment of the aqueous phase with a penicillin acylase and isolation of the 6-APA from the thus-obtained conversion solution by crystallization. Further improvements comprise extraction of the side chain to an organic solvent and isolation of 6-APA from the thus-obtained aqueous phase using a specific crystallization process.

Abstract: A first compound is converted to a second compound enzymatically in a solvent mixture containing water and a fluorinated, non-chlorinated alkane, alkene, or alkyne having up to 4 carbon atoms. Lactams, for example 6-aminopenicillanic acid (6-APA), may be prepared by enzymatic conversion of a first compound, for example penicillin-G, in a solvent mixture comprising water and a non-aqueous organic solvent, for example 1,1,1, 2-tetrafluoroethane. The 6-APA can be caused to precipitate, isolated by filtration and optionally derivatized to produce a desired compound. A by-product of the enzymatic conversion, for example phenylacetic acid, can be isolated by solvent extraction, suitably using a solvent which also comprises 1, 1, 1, 2-tetrafluoroethane.

Abstract: An enzyme membrane reactor is designed to enhance the production efficiency of foods, pharmaceutical products, and other bioproducts. The reactor is formed of a cap and a container in which a plurality of the biocatalyst-immobilized sheets are located at an interval. The reactor works in such a way that a liquid reaction mixture is introduced into the container via an inlet of the container, thereby resulting in the synthesis of a bioproduct mixture which is collected via an outlet of the reactor. The immobilized biocatalyst is prepared by entrapping a biocatalyst with a gluten matrix. The immobilized biocatalyst is deposited on supporting meshes contained by a plurality of frames that are inserted in a plurality of pairs of grooves contained by two opposite side walls of the container. Deactivated biocatalyst-immobilized sheets are replaceable and recyclable.

Abstract: The present invention describes the use of chemically defined media for the fermentative production of valuable compounds on an industrial scale. Microbial strains which are suitable for fermentation on an industrial scale using a chemically defined medium include fungal, yeast and bacterial strains. Suitable strains can be obtained as wild type strains or by screening and selection after mutagenic treatment or DNA transformation.

Abstract: DNA comprising a regulatory gene for clavulanic acid biosynthesis. DNA is no greater than 7 kb in length and has the configuration of restriction sites shown in FIG. 1 or a fragment thereof. Use of DNA in a method for producing clavulanic acid in a host.

Abstract: The invention relates to a process for the preparation of ampicillin in which 6-aminopenicillanic acid (6-APA) is subjected to an enzymatic acylation reaction with the aid of a phenylglycine derivative, with the total concentration of the 6-APA present in the reaction mixture, plus ampicillin, being greater than 250 mM, the concentration of 6-APA in solution being kept lower than 300 mM and the molar ratio of acylation agent to 6-APA which is employed being less than 2.5.

Abstract: A method and system for manipulating or modifying identifiable objects in a standard broadcast or Internet-based multimedia stream according to a control specification and a content specification. Viewers and/or organizations can independently specify acceptable levels of content on multiple dimensions to satisfy the content specification while minimizing the filtering or blocking to the viewers. A “fuzz ball” control specification is provided for masking some portion of a video frame. Several fuzz ball specifications can be overlaid to address multidimensional content specifications or rating systems. The manipulation of the multimedia stream can take place at the client (set-top box or computer), intermediate node, the content server or a combination thereof. Proxy servers can modify content specifications for outgoing requests, enabling organizations to specify intranet-wide policies.

Abstract: Process for the preparation of a &bgr;-lactam antibiotic in which a &bgr;-lactam nucleus is subjected to an enzymatic acylation reaction with the aid of an acylation agent at a molar ratio of acylation agent/&bgr;-lactam nucleus of less than 2.5, with the acylation agent and/or the &bgr;-lactam nucleus being supersaturated in the reaction mixture during at least part of the acylation reaction. In the process, a concentrated slurry or solution, for instance, of the &bgr;-lactam nucleus and/or the acylation agent with a different pH or a higher temperature than the pH or temperature at which the acylation reaction is carried out is added to the reaction mixture during the acylation reaction. Both the &bgr;-lactam nucleus and the acylation agent may be supersaturated in the reaction mixture.

Abstract: The present invention relates to a modified enzyme of a non-heme iron (II) dependent family of oxygenases and oxidases which renders the enzyme dependent on bicarbonate for activity. In a preferred embodiment, the modification is an arginine, lysine, or other amino acid that is two amino acid residues upstream of a histidine residue that is an iron ligand in the enzyme and is one of the histidine residues of the 2-histidine-1-aspartic acid trifacial motif. In particular, the modified enzymes are isopenicillin N synthetase, deacetoxycephalosporin C synthetase, and deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase which are used to make antibiotics. The present invention further provides a method for making antibiotics using a modified enzyme such as isopenicillin N synthetase, deacetoxycephalosporin C synthetase, and deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase wherein the modification renders the enzyme dependent on bicarbonate for activity.

Abstract: DNA encoding the gene for the synthetase enzyme capable of generating &dgr; (L-a-aminoadipyl)-L-crysteinyl-D-valine (ACV) from its constituent amino acids was obtained from several penicillin and cephalosporin producing organisms, e.g. Penicillium chrysogenum, cephalosporium and a Flavobacterium species. The DNA was used to prepare recombinant vectors comprising the ACV synthetase gene and hosts transformed with such vectors. The ACV synthetase gene can form part of a gene cluster comprising other genes involved in -&bgr;-lactam biosynthesis and the production of penicillin by expression of the entire biosynthetic gene cluster for the synthesis of penicillin from primary amino acids is described. Suitable hosts in which expression can take place include heterologous hosts which are naturally non-producers of penicillin.

Abstract: An isolated DNA encoding phenyl acetyl-CoA-ligase and a process of increasing the production of penicillin G in a strain of Penicillium chrysogenum by transforming the strain with the isolated DNA. Also vectors and host organisms having the isolated DNA.

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: The present invention relates to the biosynthesis of &bgr;-lactam antibiotics. More specifically, the invention relates to processes of producing &bgr;-lactam antibiotics in vivo and in vitro. Also contemplated is a novel enzyme capable of catalyzing certain steps involved in &bgr;-lactam biosynthesis. Further, the invention relates to a DNA construct encoding the novel enzyme, a recombinant vector or transformation vehicle comprising the DNA construct, and finally a cell comprising the DNA construct or recombinant vector.

Abstract: The present invention provides a method for targeting toxic antimetabolites to gram negative infections. It provides a means of taking advantage of a key disease resistance mechanism to activate these drugs locally, and to overcome the resistance phenotype of the microbes. The invention further provides a method for selecting for antibiotic sensitivity, since a likely mechanism by which organisms are likely to gain resistance to the prodrugs is via loss of enzyme activity, which will make the bacteria sensitive to antibiotics once again.

Abstract: Disclosed is a process for the synthesis of .beta.-lactam antibacterials using soluble side chain esters in the presence of enzyme acylase. Also disclosed are novel esters useful as reactants in said process.

Abstract: Degradable polyesters useful in packaging, packing, agricultural, biomedical, and other applications are made by reacting amine-protected glutamic acid with diols or epoxy compounds. The polyesters include a thermoplastic main chain aliphatic polyester, a thermoset heterochain polyester and a thermoset heterochain aromatic polyester. Each of these polyesters can be hydrolyzed into monomers using a biological catalyst such as the enzyme lipase. The thermoplastic main chain aliphatic polyester and the thermoset heterochain polyester can be degraded to respiratory gases and biomass with a mixed culture of Rhizopus chinesis, Rhizopus delemar, Penecillium pinophilum, Aspergillus niger and Pseudomonas aeruginosa microorganisms. This mixed culture of microorganisms can also be used to degrade other polyesters containing hydrolyzable backbone polyesters.

Abstract: Alternative process for obtaining 6-aminopenicillanic acid. The process comprises replacing the stages of extraction with organic solvents and isolation and separation of the intermediate penicillin salt as a solid by a process of ultrafiltration of the culture broth in at least 2 successive stages. The first stage has a cut-off for molecular weights of 20,000 Dalton and the second, 2000 Dalton. Subsequent to the enzyme conversion stage the products from that stage are subjected to a series of anionic exchange chromatography steps.

Abstract: A batch fermentation is carried out continuously or semicontinuously using strain of Streptomyces clavuligerus for the production of clavulanic acid. The fermentation process is carried out with strict control of the soluble phosphate in the medium both at the beginning and throughout the process.

Abstract: A lactamase enzyme having good stability, capable of hydrolysing an enatiomer of the bicyclic lactam, 2-azabicyclo[2.2.1]hept-5-en-3-one, to give (-) lactam and (+) amino acid, has been found in a strain of Comamonas acidivorans. The enzyme has been isolated and cloned, and its structure identified.

Abstract: A process is taught for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via enzymatic ring expansion activity on penicillin G, using a Penicillium chrysogenum transformant strain expressing expandase.

Abstract: The present invention relates to the biosynthesis of .beta.-lactam antibiotics. More specifically, the invention relates to processes of producing .beta.-lactam antibiotics in vivo and in vitro. Also contemplated is a novel enzyme capable of catalyzing certain steps involved in .beta.-lactam biosynthesis. Further, the invention relates to a DNA construct encoding the novel enzyme, a recombinant vector or transformation vehicle comprising the DNA construct, and finally a cell comprising the DNA construct or recombinant vector.

Abstract: Disclosed is a process for the synthesis of .beta.-lactam antibacterials using soluble side chain esters in the presence of enzyme acylase. Also disclosed are novel esters useful as reactants in said process.

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: The invention relates to an improved process for the production of a secondary metabolite comprising (i) fermentation of a microorganism capable of producing said secondary metabolite, and (ii) recovering said metabolite in substantially pure form. Said microorganism has been modified in a manner whereby the expression of one or more of the DNA sequences coding for (a) peptide(s), (a) protein(s) or (an) enzyme(s), involved in or interfering with the biosynthetic pathway of said secondary metabolite, is regulated differently from the regulation of said DNA sequence(s) in the original microorganism. Further contemplated is a process for production of said microorganism, a DNA construct, a vector or transformation vehicle, a microorganism capable of producing secondary metabolite and finally a secondary metabolite product.

Abstract: Novel methods and compositions are provided for the enhanced production of .beta.-lactam antibiotics. The process is exemplified by the production of penicillin. In addition, the P. chrysogenum and A. chrysogenum .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase genes have been isolated and sequenced. Also methods are provided for the production of .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine synthetase using recombined DNA techniques.

Abstract: The invention relates to an improved process for preparing cephalosporins by reaction compounds such as 7-amino-cephalosporanic acid, 7-amino-3-deacetoxy-cephalosporanic acid or their derivatives with derivatives of .alpha.-amino acids in the presence of a properly immobilized penicillin acylase enzyme under the following conditions, independently, or in combination: (1) at a temperature ranging from 0.degree. C. to +20.degree. C.; or (2) at ambient pH; with a high molar ratio of .alpha.-amino acid to a cephalosporanic nucleus.

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 chemical analyzer has turn tables respectively carrying reaction vessels, sample containers and reagent containers disposed thereon in circular rows. A sample pipetting mechanism and a reagent pipetting mechanism are provided to transfer predetermined amounts of sample and reagent solution from a sample container and from a reagent container into a reaction vessel. The thus transferred sample and reagent solution are mixed in the reaction vessel by a stirrer comprising a piezoelectric element which is disposed in non-contacting relationship to the sample and reagent solution in the reaction vessel and is electrically energized to generate a sound wave which causes a circulating flow of the reagent solution in the reaction vessel whereby the sample and the reagent solution are mixed in a non-invasive manner.

Abstract: The present invention is directed to a gene which is related to a D-N-carbamoyl-.alpha.-amino acid amidohydrolase which is an enzyme capable of converting D-N-carbamoyl-.alpha.-amino acids into D-.alpha.-amino acids; a recombinant plasmid in which a DNA fragment containing the gene is incorporated into a vector; a microorganism belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Corynebacterium, or Brevibacterium, which is transformed by incorporating the recombinant plasmid thereinto; a process for the production of D-N-carbamoyl-.alpha.-amino acid amidohydrolases, comprising the steps of cultivating the transformed microorganism and collecting the desired product therefrom; a D-N-carbamoyl-.alpha.-amino acid amidohydrolase obtained by the method; and a process for the production of D-.alpha.-amino acids with the aid of an action of the enzyme.The D-N-carbamoyl-.alpha.-amino acid amidohydrolase can be fixed on a support for immobilization and used as an immobilized enzyme.

Abstract: The invention provides a process for the preparation of the compound of formula I ##STR1## wherein R is carboxy group or a carboxylate anion, by enzymatic hydrolysis with a lipase or an acylase in an alcoholic solution, of a compound of the formula II ##STR2## wherein R.sub.1, represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group, and R.sub.2 is a hydrogen atom, an alkyl, alkenyl, phcnyl, phenylalkyl or phenylalkenyl group having from 1 to 18 carbon atoms or an alkoxy group.

Abstract: The present invention is directed to a gene which is related to a D-N-carbamoyl-.alpha.-amino acid amidohydrolase which is an enzyme capable of converting D-N-carbamoyl-.alpha.-amino acids into D-.alpha.-amino acids; a recombinant plasmid in which a DNA fragment containing the gene is incorporated into a vector; a microorganism belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Corynebacterium, or Brevibacterium, which is transformed by incorporating the recombinant plasmid thereinto; a process for the production of D-N-carbamoyl-.alpha.-amino acid amidohydrolases, comprising the steps of cultivating the transformed microorganism and collecting the desired product therefrom; a D-N-carbamoyl-.alpha.-amino acid amidohydrolase obtained by the method; and a process for the production of D-.alpha.-amino acids with the aid of an action of the enzyme.The D-N-carbamoyl-.alpha.-amino acid amidohydrolase can be fixed on a support for immobilization and used as an immobilized enzyme.

Abstract: The invention relates to an improved process for converting 6-acylaminopenicillanic acid (6-AAPA) to 6-aminopenicillanic acid (6-APA). The process employs a solution or suspension of penicillin acylase from which the product is separated after reaction by ultrafiltration through a particular class of polymer membranes. The process of the invention may also be applied to the production of 7-aminodesacetoxycephalosporanic acid (7-ADCA) and can be incorporated into an improved, streamlined process for obtaining 6-APA from fermentation broths.

Abstract: Targeted gene insertion methodology can increase the production of an antimicrobial metabolite and comprises the steps of:a) identifying the gene in unaltered chromosomal DNA which encodes an enzyme that catalyzes the rate controlling step in a biosynthetic pathway in the production of increased concentration of a precursor to a core molecule which leads to the antimicrobial metabolite; andb) inserting into unaltered chromasomal DNA a genetic delivery vehicle (such as a vector, phage, or virus) which carries a gene which encodes the enzyme that catalyzes the rate controlling step in the biosynthesis in the production of a core molecule which is a precursor to the antimicrobial metabolite into unaltered chromosomal DNA, said delivery vehicle being compatible with said unaltered chromosomal DNA, the delivery vehicle being generated byinserting at least one exact or modified copy of the gene determining the rate controlling step into the compatible delivery vehicle, andinserting the delivery vehicle containing t

Abstract: N-Terminal .beta.,.gamma.-didehydrovaline di- and tri-peptides are reacted with isopenicillin N synthetase to form 3-exomethylenecepham-4-carboxylic acids, e.g., .delta.-(L-.alpha.-aminoadipoyl)-L-cysteinyl-D-.beta.,.gamma.-didehydroval ine is incubated with the purified enzyme to provide 7.beta.-(L-.alpha.-aminoadipoylamino)-3-exomethylenecepham-4-carboxylic acid. The 3-exocepham products are useful intermediates to 3-alkoxy-3-cephem and the 3-halo-3-cephem antibiotics.

Abstract: The present invention provides isolated DNA compounds and recombinant DNA cloning and expression vectors that encode PNB esterase from Bacillus subtilis. The invention also provides host cells transformed with these vectors and a method for production of the PNB esterase by recombinant DNA techniques.

Abstract: This invention discloses novel immunogenic peptide sequences, derived from the human cyclooxygenase-1 and cyclooxygenase-2 cDNAs which elicit specific non cross-reactive antibody responses. Assays are also disclosed for selectively and independently detecting cyclooxygenase-1 or cyclooxygenase-2 proteins present in a given biological sample.

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: A process for fabricating a high-reliability composite dielectric layer (19) includes the formation of a first oxynitride layer (14) on the surface (12) of a silicon substrate (10). The formation of the first oxynitride layer (14) is followed by an oxidation step to form a silicon dioxide layer (16) at the surface (12) of the substrate (10) and underlying the first oxynitride layer (14). The composite dielectric layer (19) is completed by exposing the substrate (10) to nitrous oxide, and diffusing a nitrogen bearing species through both the silicon dioxide layer (16) and the first oxynitride layer (14) to form a second oxynitride layer (18) underlying the silicon dioxide layer (16). The composite dielectric layer (19) exhibits a nitrogen-rich region at the interface between second oxynitride layer (18) and the silicon substrate (10). A second nitrogen rich region is also formed near the surface of the first oxynitride layer (14).

Abstract: An in vitro process for preparing 6((1R)-hydroxyethyl) penem acids by hydrolyzing the carboxylic ester derivative thereof using an enzyme capable of selectively hydrolyzing the ester group at the 3-position of the carboxylic acid ester using an esterase, acylase or lipase enzyme, wherein the enzymatic hydrolysis is effected at a pH in the range of from 5 to 8 and at a temperature in the range of 20.degree. C. to 40.degree. C.

Abstract: A method for the selective separation of a particular compound from a mixture of compounds, by enzymatically converting a weakly adsorbable compound to a strongly adsorbable compound, and binding the converted compound to a material of appropriate chemical properties is described. Also described are methods for removing contaminants from wastewater streams, and from intermediate chemical process streams.

Abstract: A GL-7ACA acylase having the following characteristics:(a) has ability to catalyze the enzymatic conversion of glutaryl 7-ACA, adipyl 7-ACA, and succinyl 7-ACA, into 7-aminocephalosporanic acid,(b) has a molecular weight of 70,000 dalton (SDS-PAGE) and(c) has N-terminal amino acid sequence (SEQ ID NO: 1) thereof: Gln-Ser-Glu-Gln-Glu-Lys-Ala-Glu-Glu-.A process for producing GL-7ACA acylase is also provided.

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.