Abstract: A three-dimensional structure is described of a complex of isopenicillin N synthase (IPNS) with Fe and its substrate ACV. This structure is used to design modified enzymes IPNS, DAOCS, DACS, DAOC/DACS and other related enzymes of the penicillin and cephalosporin biosynthesis pathway, which modified enzymes may accept unnatural substrates or improve production efficiency or produce improved products. Specific modifications of specific amino acid residues are proposed and exemplified.

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: There is described a process for producing exomethylene cepham intermediates useful in cephalosporin chemistry. The process comprises the preparation of a compound of the formula ##STR1## in which R.sup.1 is an amino group, a protected amino group, an acylamino group or a diacylamino group,R.sup.2 is hydrogen, C.sub.1-4 alkoxy or C.sub.1-4 alkylthio,R.sup.3 is hydrogen, a salt ion or an ester-forming group, andR.sup.4 is hydrogen or C.sub.1-3 alkyl,by reacting a compound of the formula ##STR2## in which Y is a bridging group of the formula ##STR3## Z is chloro, bromo or iodo, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the above defined values, with a reagent providing cobalt I, under reducing conditions.

Abstract: A compound of formula II: ##STR1## wherein R is hydrogen or an alkyl group and R' is an alkoxy group, and salts and esters thereof.

Abstract: 2-(Allenyl)penicillins antibiotics and intermediates thereto are disclosed. A process for making the 2-(allenyl)penicillins and the starting materials for the process are also disclosed.

Abstract: A compound of formula I or a physiologically acceptable salt thereof ##STR1## wherein X represents sulphur or methylene, R.sub.1 represents hydrogen, amino or an acylated or carbamylated amino group, R.sub.2 represents hydrogen or an alkyl group and R.sub.3 represents an alkoxy group.

Abstract: 6.beta.-(L-.alpha.-Aminoadipoyl)-2.alpha.-vinyl-2.beta.-methylpenam-3-carbo xylic acid is provided in an enzymatic process converting .delta.-(L-.alpha.-aminoadipoyl)-L-cysteinyl-D-.gamma.,.delta.-didehydrois oleucine with isopenicillin N synthetase. The 2.alpha.-vinylpenam product is converted by known methods to the 6.beta.-amino-2.alpha.-vinyl-2.beta.-methylpenam-3-carboxylic acid nucleus and the latter is N-acylated to provide corresponding 6.beta.-acylaminopenams.

Abstract: A cell-free process for converting isopenicillin N, .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine (hereinafter "LLD") and 6-substituted derivatives thereof to deacetoxycephalosporin C (DACPC) by the following reaction sequence: ##STR1## is disclosed. In addition to the starting material, the reaction system includes ATP and a fresh extract of Cephalosporium acremonium prepared and used in a manner to preserve the racemase agent or agents necessary for conversion of the isopenicillin N to penicillin N, a necessary intermediate step in the process.

Abstract: Isopenicillin derivatives having antimicrobial properties and a general formula of: ##STR1## where R, R.sub.1, and R.sub.2 are hydrogen, methyl, ethyl, propyl, isopropyl, or halogenated methyl, ethyl, propyl or isopropyl radicals and R.sub.3 is ##STR2## are produced in a cell-free system using an extract from Cephalosporium acremonium. The starting materials for the synthesis consist of tripeptides composed of unsubstituted or .beta.-substituted D-valine, unsubstituted or substituted L cysteine, and L- .alpha.-aminoadipic acid or its analogues. Certain enzymes in the cell-free extract are inactivated so that conversion does not proceed past the isopenicillin stage.

Abstract: This invention provides novel .beta.-lactam precursors of known and novel microbiologically active penicillins and cephalosporins and to a process for making the .beta.-lactam precursors from a L-cysteinylvaline dipeptide or a polypeptide containing the L-cysteine with other amino acids. The .beta.-lactam precursors are represented by the Formula I. ##STR1## wherein Z is ##STR2## and wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are defined herein. When Z has the structure of Formula A, the .beta.-lactam is a precursor for cephalosporins. When Z has the structure of either Formula B or Formula C, the .beta.-lactam is a precursor for a penicillin.