Mer-WF3010, a new member of the papulacandin family. I. Fermentation, isolation and characterization.

Mer-WF3010, a new member of the papulacandin family, was isolated from the mycelia of Phialophora cyclaminis Mer-WF3010 (FERM P-11475). The molecular formula of Mer-WF3010 was determined as C45H60O16.

Enzymatic dimerization of penicillin X.

Penicillin X methyl ester was transformed into three types of dimer by laccase from Coriolus versicolor. The dimers are considered to be formed by free-radical addition of phenoxy radicals produced by laccase. The enzyme reaction with the ester as substrate was more suitable for forming dimers than that with the sodium salt as substrate. Penicillin X pivaloyloxymethyl ester was also transformed into a dimer, which had antibacterial activity in the presence of esterase.

Mutagenesis of OA-6129 carbapenem-producing blocked mutants and the biosynthesis of carbapenems.

Streptomyces fulvoviridis A933 17M9 1501 is an A933 acylase-defective mutant derived from S. fulvoviridis A933 17M9 and thus produces the OA-6129 group of carbapenems and carbapenams. By further mutation of mutant 1501, 4 types of mutants (OA-6129 A + B1 + B2 producers; OA-6129 A + B2 producers; an OA-6129 A producer; non-producers) were obtained. The second type of mutant strains 4N 3607, 5NA 3949-40 and 5NE 252 proved useful for the fermentative production of carbapenem OA-6129 B2. These results of mutagenesis demonstrated that the sequence of carbapenem bioconversion in the horizontal route was hydroxylation at C-8----isomerization at C-6----sulfation at C-8 hydroxyl.

Pharmacological studies on carbapenem antibiotics. I. Metabolism of PS-5 in animal tissues.

After injection into mice and dogs, PS-5 showed a very rapid decrease in its blood concentration, compared with cefazolin. Using in vitro experiments with tissue homogenates and acetone powder preparations, the kidney was found to be the primary site of PS-5-inactivation, although the extent of the inactivation varied depending on the species of animals. The comparative stability data of PS-5, NS-5 (deacetylated PS-5), thienamycin and N-formimidoylthienamycin in kidney homogenates of mouse, rabbit, dog and man are presented. Bilateral nephrectomy and the injection of ethylenediaminetetraacetate seemed to prolong the survival time of PS-5 in rats and mice respectively.

Pharmacological studies on carbapenem antibiotics. II. Isolation of a PS-5-inactivating factor from the rat kidney.

A factor responsible for the in vivo metabolism of PS-5 was isolated from the microsomal fraction of the rat kidney. This factor, which did not attack penicillins and cephalosporins, was enzymologically identified with particle-bound renal dipeptidase. Under the action of this factor, PS-5 was inactivated to give three products designated PS-5D I, PS-5D II and PS-5D III.

New anthracycline metabolites from mutant strains of Streptomyces galilaeus MA144-M1. II. Structure of 2-hydroxyaklavinone and new aklavinone glycosides.

Four blocked mutants of aclacinomycin-producing Streptomyces galilaeus MA144-M1 produced new anthracyclinones; 2-hydroxyaklavinone, its non-esterified analog and 2-hydroxy-7-deoxyaklavinone, several new anthracyclines; 2-deoxyfucosyl-2-deoxyfucosyl-rhodosaminylaklavinone (MA144 U1), 2-deoxyfucosyl-rhodosaminylaklavinone (MA144 U2) and five aklavinone glycosides devoid of amino sugar, designated as MA144 U5, U6, U7, U8 and U9.

PS-6 and PS-7, new beta-lactam antibiotics. Isolation, physicochemical properties and structures.

Antibiotics PS-6 and PS-7 which are shown to be 5R,6R-3-(2-acetamido)ethylthio-6-isopropyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid and 5R,6R-3-(E)-(2-acetamido) vinylthio-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid respectively, are new beta-lactam compounds isolated from fermentation broths of Streptomyces cremeus subsp. auratilis A271, S. fulvoviridis A933, S. olivaceus ATCC 31126 and S. flavogriseus NRRL 8139. Fermentation, isolation, physicochemical properties and structures of antibiotics PS-6 and PS-7 are described.

PS-6 and PS-7, new beta-lactam antibiotics. In vitro and in vivo evaluation.

Biological properties of two new beta-lactam antibiotics, PS-6 and PS-7, containing the carbapenem nucleus were studied. The in vitro activities of PS-6 and PS-7 were tested against clinical isolates of Gram-positive and Gram-negative bacteria in comparison with those of cefazolin, ampicillin and PS-5. In general, the antibacterial spectra of PS-6 and PS-7 were similar to that of PS-5. PS-7 was slightly less active than PS-5 and ABPC against Staphylococcus aureus. Clinical isolates of Gram-negative bacteria were found to be 2- to 8-fold more resistant to PS-6 than to PS-5, while PS-7 was 2-fold more active than PS-5 against Enterobacter, Klebsiella, Proteus, Serratia and Escherichia coli. The therapeutic effect of PS-6 seemed slightly less than that of PS-5 in an experimental infection with Staph. aureus Smith in mice.

Antitumor anthracycline antibiotics, aclacinomycin A and analogues. I. Taxonomy, production, isolation and physicochemical properties.

Aclacinomycin A and B, two major components of a new antitumor antibiotic complex, and their 19 analogues were produced by a culture of strain No. MA144-M1, which was identified as Streptomyces galilaeus. They were isolated by chelation with copper ion and silicic acid chromatography, and characterized by physicochemical methods in the anthracycline group of antibiotics.

PS-5, a new beta-lactam antibiotic. I. Taxonomy of the producing organism, isolation and physico-chemical properties.

Antibiotic PS-5 is a new beta-lactam antibiotic isolated from fermentation broths of Streptomyces sp. strain A271. The strain was considered to be a new subspecies of Streptomyces cremeus and the name, Streptomyces cremeus subsp. auratilis, was proposed. Fermentative production, isolation and physico-chemical properties of PS-5 are described.