Abstract: An isolated DNA having the promoter sequence of the hex gene of P. chrysogenum or a DNA fragment that is hybridizable to the complement of the promoter sequence under stringent conditions and is capable of directing expression of DNA downstream of the fragment in P. chrysogenum. Also a process for promoting expression of a coding sequence of interest in a microorganism using the isolated DNA and a process to block expression of a gene of interest in a microorganism using the isolated DNA are disclosed.

Abstract: The invention relates to the process for the isolation of a pharmaceutically acceptable alkali metal salt of clavulanic acid from a fermentation broth containing impure clavulanic acid comprising the steps of filtration of the fermented broth, extraction of the clavulanic acid to a water immiscible or partly water immiscible solvent at pH from 1.2-2, precipitation of an alkali metal salt A of clavulanic acid by addition of a solution of an alkali metal alkylalkanoate, characterized by the following steps: before the filtration the fermented broth containing clavulanic acid is diluted with water, a flocculating agent is added and the pH is adjusted to 3-5 for further purification the alkali metal salt A of clavulanic acid is converted to clavulanic acid by addition of an inorganic acid and is extracted into a water immiscible or partly water immiscible solvent a solution of a different alkali metal B alkyl alkanoate is added and the alkali metal salt B of clavulanic acid is precipitated.

Abstract: The invention relates to promoters of the genes glutamate dehydrogenase, &bgr;-acetylhexosaminidase and &ggr;-actin and their use in systems of expression, secretion and anti-sense of filamentary fungi. The invention also relates to the use of the promoters of the genes which code: (I) glutamate dehydrogenase NADP depending (EC.1.4.1.4) of Penicillium chrysogenum, (II) &ggr;-N-actylhexosaminidase (EC.3.2.1.52) of Penicillium chrysogenum and (III) &ggr;-actin of Penicillium chrysogenum and Acrimonium chrysogenum, which can be used for the construction of potent vectors of expression and secretion useful both for P. chrysogenum and for A. chrysogenum and related species. These promoters can also be used for blocking the genic expression through anti-sense construction. Under the control of the above mentioned promoters, it is possible to conduct the expression of other genes in filamentary fungi, thereby increasing the production of antibiotics and/or proteins inherent to the same.

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: 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: Process for purifying 7-substituted aminodeacetoxycephalosporins through the use of filter membranes. A process for purification by ultrafiltration and/or nanofiltration with a cut-off for molecular weights over 10,000 Dalton and preferably over 2000 Dalton is described. For example cephalosporin-G of increased purity, represented by a 6-8% increase in the HPLC titre, with a reduction of 50% in absorbance, is obtained using this technique. The invention makes it possible for the purified products to be used directly in the synthesis of other antibiotic compounds without the need for intermediate isolation.

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: The process comprises a series of stages essentially comprising the protection of the functional groups of the side chain of Ampicillin, esterification of the acid group, oxidation to sulphoxide, expansion of the thiazole ring to a thiazine ring, ozonolysis of the exomethylene cefam derivative obtained, substitution of the hydroxyl group by chlorine and de-protection of the functional groups, in which the order of some stages can be varied without affecting the final result.

Abstract: A drug resistant strain of P.chrysogenum has said drug resistance conferred by heterologous DNA, in particular a heterologous gene(s) under the control of a Penicillium control sequence(s). Drug resistance is especially to sulfonamides, or to trimethoprim or methotrexate by a gene derived from plasmid R388. A vector capable of conferring resistance to methotrexate or sulfonamide on P.chrysogenum, comprises at least one said resistance gene under the control of trpC controlling sequences.

Abstract: A new hybrid plasmid vector suitable for transforming microorganisms of the genus Escherichia. This plasmid vector confers sucrose fermenting capacity to E. coli K12 cells. The plasmid vector may also be useful for carrying additional genetic information capable of controlling the production of commercially useful chemical compounds. Fermentation cultures of the microorganisms containing this plasmid vector may be propagated in a medium containing sucrose as the main carbon source, thereby increasing the plasmid stability.

Abstract: Sodium amoxycillin, of use for example by parenteral administration, is prepared by:(a) suspending amoxycillin trihydrate in a mixture comprising an aprotic organic solvent and a lower alcohol;(b) solubilizing the amoxycillin trihydrate by the addition of a low molecular weight amine of the group of cyclic or heterocyclic aliphatics;(c) adding to such solution the sodium salt of diethyloxalacetic acid, agitating the reaction mixture at a temperature of from -10.degree. C. to ambient temperature and finally isolating the sodium amoxycillin by filtration after its precipitation in the reaction medium by the addition of an aprotic organic solvent.

Abstract: Novel salts of the formula ##STR1## are disclosed wherein n is 1 or 2; both OR groups are O.sup.- when n is 2, or one is O.sup.- and one is OH when n is 1; and R.sub.1, R.sub.2, R.sub.3, and R.sub.4 independently represent hydrogen, alkyl, aryl, amino-alkyl, hydroxy-alkyl, or hydroxy-alkyl-amino. These salts are useful in treatment of microbial infecting in mammals, and use of the salts in composition for oral and parenteral administration is also disclosed.

Abstract: A process for the preparation of alpha-(N-pyrrolyl)-derivative acids, the salts and esters thereof, of the formula ##STR1## in which R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are hydrogen atoms or substituted or unsubstituted alkyl, aryl, alkylaryl or heterocyclic radicals and R' is a metal cation, an organic base or an organic radical, wherein the corresponding amino ester is reacted with a dialkoxytetrahydrofuran or a derivative thereof. Certain compounds comprised among those corresponding to the above formula, particularly the DL, D and L-alpha-(N-pyrrolyl)-phenylacetic acids and certain esters thereof. Therapeutical compositions containing such compounds as active ingredient and therapeutical applications of said compounds.

Abstract: A process for the activation of carboxylic acids which is useful for the subsequent conversion of said carboxylic acids into their corresponding amides or esters, based on reacting a 2-oxazolidinone with phosphorus pentachloride and subsequent addition of a salt of the carboxylic acid to be activated.