Modified expandase and its uses

A technology of penicillin and residues, applied in the field of penicillin N expandase, which can solve problems such as poor substrates

Inactive Publication Date: 2007-05-16
ORCHID CHEM & PHARM LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, penicillin G is a poor su

Method used

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  • Modified expandase and its uses
  • Modified expandase and its uses
  • Modified expandase and its uses

Examples

Experimental program
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Embodiment Construction

[0019] The present invention provides mutant penicillin expandases which exhibit increased or modified ring expansion activity, preferably towards penicillin G or penicillin V as substrates, compared to the wild type expandase.

[0020] The mutant penicillin expandases according to the present invention include expandases derived from Streptomyces clavulatus or expandases derived from other organisms.

[0021] The nucleotide and amino acid sequence of the penicillin N expandase from Streptomyces clavulilis is shown in SEQ ID NO: 1 (Figure 1).

[0022]A first aspect of the present invention is to provide a mutated penicillin expandase with better substrate specificity for penicillin G or penicillin V, wherein the mutated penicillin expandase is at one or more of the residue positions corresponding to the wild-type expandase An amino acid substitution is included at a residue position selected from threonine at position 42, isoleucine at position 50, histidine at position 57, th...

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Abstract

The present invention relates to a mutant penicillin expandase which comprises an amino acid substitution at one or more residue positions corresponding to those of a wild-type expandase selected from the group consisting of threonine at position 42, isoleucine at position 50, histidine at position 57, threonine at position 67, valine at position 133, threonine at position 143, proline at position 145, glycine at position 148, phenyl alanine at position 152, proline at position 196, alanine at position 240, cysteine at position 281, Serine at position 309, provided that the amino acid substitution at the residue position of cysteine at position 281 is not tyrosine.

Description

field of invention [0001] The present invention relates to modified expandases, particularly penicillin N expandases having increased specificity for substrates such as penicillin G. Background of the invention [0002] β-Lactam antibiotics occupy a major part of the anti-infective field due to low toxicity, high specificity and clinical efficacy against a wide variety of pathogenic organisms. Many organisms within bacterial and fungal species produce traditional β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and unconventional antibiotics such as clavulanic acid and thanamycin. Penicillium chrysogenum and Cephalosporium acremonium of the fungal family produce penicillin G and cephalosporin C, respectively. Streptomyces clavuligerus, a bacterium that produces the traditional antibiotic cephamycin and the unconventional antibiotic clavulanic acid, is known for its beta-lactamase inhibition. Reference may be made to reviews such as Jensen, S.E. & Dema...

Claims

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Application Information

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IPC IPC(8): C12N15/53C12N1/21
Inventor M·杜赖拉杰V·维纳亚加姆V·蒂瓦里B·阿西尔T·J·马西拉马尼M·拉温德拉纳塞恩
Owner ORCHID CHEM & PHARM LTD
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