Production of the penicillin precursor 5-(L-a-aminoadipyl)-L-cysteinyl-D-valine (ACV) by cell-free extracts from Streptomyces clavuligerus
نویسنده
چکیده
Glycerol-stabilised cell extracts of Streptomyces clavuligerus contain an enzyme activity which synthesises ACV from the individual amino acids L-a-aminoadipic acid, t-cysteine and L-valine. Enzyme activity was optimum in reaction mixtures containing 1 mM ATP together with an ATP regenerating system. The ACV synthetase enzyme formed ACV analogs when provided with Lcarboxymethylcysteine in place of L-a-aminoadipic acid or when provided with L-alloisoleucine or L-a-aminobutyrate in place of L-valine. Multistep conversion of individual amino acids to penicillin and cephalosporin antibiotics was restricted as a result of the inhibitory effects of L-c~-aminoadipic acid and L-cysteine on isopenicillin N synthetase.
منابع مشابه
CYCLIZATION OF o-(L-(C-AMINOADIPYL)-L-CYSTEINYL-D-VALINE TO PENICILLINS BY CELL-FREE EXTRACTS OF STREPTOMYCES CLAVULIGERUS
Cell-free extracts prepared by sonication of Streptomyces clavuligerus cyclized 6-(L-aaminoadipyl)-L-cysteinyl-D-valine (ACV) into a penicillin-type antibiotic. The antibacterial spectrum of this antibiotic suggested it was a mixture of isopenicillin N and penicillin N indicating that both cyclization and racemase activities were present. Cyclization activity was optimal in extracts prepared fr...
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Benzylpenicillin, a typical antibiotic produced by some species of fungi, was obtained by direct cyclization of the heteropeptide phenylacetyl-L-cysteinyl-D-valine using cell-free extracts of Streptomyces clavuligerus. This is the first description of evidence of the synthesis of benzylpenicillin from a non natural molecule using a bacterial enzyme.
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Isopenicillin N synthase (IPNS) is one of the key enzymes in the penicillin and cephalosporin biosynthetic pathway which catalyses the conversion of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N. The IPNS from Penicillium chrysogenum 23X-80-269-37-2, a high penicillin V-producer, was found to possess an isoleucine residue instead of tyrosine at position 195. An attempt to ...
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delta-(L-alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase was isolated and partially characterised from Cephalosporium acremonium CO728 and Streptomyces clavuligerus. The purification procedure resulted in a 745- and 277-fold increase in specific enzyme activity, respectively. Both enzymes had similar apparent molecular masses of ca. 300 kdaltons by SDS-polyacrylamide electrophoresis, ...
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