Enzymic and chemical transformations of the side chain of cephalosporin C

Mazzeo, Pietro; Romeo, A.

doi:10.1039/p19720002532

Cited by 27 publications

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“…Preliminary studies revealed that strain SE83 yielded 7,-(4-carboxy-5-oxopentanamido)cephalosporanic acid and 7p-(4-carboxybutanamido)cephalosporanic acid (GL-7ACA) in addition to 7ACA from cephalosporin C. These compounds have been known to be generated from cephalosporin C through oxidative deamination (11) and subsequent decarboxylation in the presence of H202 as illustrated in Fig. 1.…”

mentioning

confidence: 99%

Cloning and characterization of the genes for two distinct cephalosporin acylases from a Pseudomonas strain

Matsuda¹,

Matsuyama²,

Yamamoto³

et al. 1987

J Bacteriol

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Pseudomonas sp. strain SE83 converts cephalosporin C and 7,1-(4-carboxybutanamido)cephalosporanic acid (GL-7ACA) to 7-aminocephalosporanic acid (7ACA). A DNA library of this strain was constructed in Escherichia coli and screened for the ability to deacylate GL-7ACA to 7ACA. Apparently, two distinct genes, designated acyI and acyll, were cloned on 4.8-and 6.0-kilobase-pair BglII fragments, respectively. The enzymes encoded by the two genes showed different substrate specificities, and the acyll-encoded enzyme was found to yield 7ACA from cephalosporin C by direct deacylation. Expression of the two genes in E. coli was strongly dependent on a promoter of the vector. The coding regions for acyI and acyIl were localized on the 2.5-and 2.8-kilobase-pair fragments, respectively, by subcloning experiments, and high expression of both genes was obtained by placing them under the control of the lacUV5 promoter. The acyII-encoded enzyme was purified and shown to be composed of two nonidentical subunits with molecular weights of 26,000 and 57,000. Maxicell analysis revealed three acyIl-specific polypeptides, two of which corresponded to the above subunits. The third polypeptide with a molecular weight of 83,000 was suggested to be the precursor of both subunits.Penicillin and cephalosporin acylases (penicillin amidohydrolase EC 3.5.1.11) catalyze the deacylation of acyl side chains of penicillin and cephalosporin derivatives to yield 6-aminopenicillanic acid and 7-aminocephalosporanic acid (7ACA), respectively, key intermediates for semisynthetic 1-lactam antibiotics for medical use. Through exhaustive screening, many kinds of such activities have been detected in a wide variety of microorganisms. To our knowledge, however, enzymatic deacylation of cephalosporin C having D-a-aminoadipic acid moiety in the acyl side chain has not been confirmed despite claims for such an activity by a few patent applications.Recently, we have isolated from soil a strain of Pseudomonas sp., designated SE83, which has an activity to convert cephalosporin C to 7ACA (manuscript in preparation). Preliminary studies revealed that strain SE83 yielded 7,-(4-carboxy-5-oxopentanamido)cephalosporanic acid and 7p-(4-carboxybutanamido)cephalosporanic acid in addition to 7ACA from cephalosporin C. These compounds have been known to be generated from cephalosporin C through oxidative deamination (11) and subsequent decarboxylation in the presence of H202 as illustrated in Fig.

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mentioning

confidence: 99%

Cloning and characterization of the genes for two distinct cephalosporin acylases from a Pseudomonas strain

Matsuda¹,

Matsuyama²,

Yamamoto³

et al. 1987

J Bacteriol

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“…In addition, D-amino acids are proposed to be indicators of aging because age-related accumulation was observed in lens protein and brain tissue (Man et al, 1987;Poinar et al, 1999). As for other applications of pDAO, bioconversion of cephalosporin C to 7-amino-cephalosporanic acid (Mazzeo and Romeo, 1972), and enzymatic preparation of valuable L-amino acids (Hanson et al, 1999;Roff et al, 2004) were reported.…”

Section: Introductionmentioning

confidence: 98%

Thermostabilization of porcine kidney D‐amino acid oxidase by a single amino acid substitution

Bakke

Setoyama

Miura

et al. 2005

Biotech & Bioengineering

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D-amino acid oxidase (DAO) is of considerable practical importance, such as bioconversion and enzymatic assay. In this study, we succeeded in obtaining a thermostable mutant DAO from porcine kidney by a single amino acid substitution. This mutant enzyme, F42C, was stable at 55 degrees C, while the wild-type enzyme was stable only up to 45 degrees C. The Km values of F42C for D-amino acids was about half of those of the wild-type enzyme. This mutant DAO with improved stability and affinity for its substrates is advantageous for the determination of D-amino acids.

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“…The key intermediate in the production of these cephalosporins is 7-amino-cephalosporanic acid (7-ACA) which is derived chemically from cephalosporin C (Fechtig et al, 1968). Since the chemical process of conversion is hazardous and uses toxic chemicals, enzymatic alternatives have been looked into (Mazzeo and Romeo, 1972;Szwajcer and Mosbach, 1985). The preferred system tbr bioconversion has been a two step enzymatic process (Fig.…”

Section: Introductionmentioning

confidence: 99%

Cephalosporin modification: An extracellular glutaryl-7-ACA acylase from Bacillus sp.

1996

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Enzymic and chemical transformations of the side chain of cephalosporin C

Cited by 27 publications

References 0 publications

Cloning and characterization of the genes for two distinct cephalosporin acylases from a Pseudomonas strain

Cloning and characterization of the genes for two distinct cephalosporin acylases from a Pseudomonas strain

Thermostabilization of porcine kidney D‐amino acid oxidase by a single amino acid substitution

Cephalosporin modification: An extracellular glutaryl-7-ACA acylase from Bacillus sp.

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