Novel compounds

Abstract

DNA sequences obtained from S. clavuligerus ATCC 27064, recombinant vectors incorporating such sequences and hosts transformed with such vectors are disclosed. The DNA comprises one or more genes coding for one or more enzymes involved in the biosynthesis of penicillin and cephalosporin β-lactams and such enzymes are expressed by hosts into which the recombinant vectors are transformed. The DNA and the enzymes encoded thereby have utility in the preparation of penicillins and cephalosporins, both known and novel, possessing pharmacological, especially antimicrobial, activity.

1 . DNA (I) or a restriction fragment derived therefrom containing one or more genes coding for one or more enzymes involved in the biosynthesis of penicillin and cephalosporin β-lactams, the said DNA having the configuration or restriction sites shown in FIG. 1( a ).  
     
     
         2 . DNA according to  claim 1  having the configuration of restriction sites shown in any one of FIG. 1( b ), FIG. 1( c ) or FIG. 1( d ).  
     
     
         3 . A recombinant vector comprising a DNA sequence according to  claim 1   
     
     
         4 . A recombinant vector comprising a DNA sequence as claimed in  claim 1  cloned into a plasmid derived from a Streptomycete or a temperate phage.  
     
     
         5 . A recombinant vector according to  claim 4  in which the plasmid is pIJ 702.  
     
     
         6 . A recombinant vector according to  claim 4  selected from the group consisting of pBROC 137 , pBROC 138 and pBROC 303.  
     
     
         7 . A host transformed with at least one recombinant vector as claimed in  claim 3 .  
     
     
         8 . A host according to  claim 7  in which the host is a Streptomycete.  
     
     
         9 . A host according to  claim 7  in which the host is  S. lividans  66 (DSM 1567).  
     
     
         10 . The isopenicillin N synthetase enzyme of  S. clavuligerus  ATCC 27064, or any other protein capable of converting δ (L-α-aminoadipyl)-L-cysteinyl-D-valine into isopenicillin N, when produced by a transformed host as claimed in  claim 7 .  
     
     
         11 . The penicillin N synthetase enzyme of S. clavuligerus ATCC 27064, or any other protein capable of converting isopenicillin N into penicillin N, when produced by a transformed host as claimed in  claim 7 .  
     
     
         12 . The deacetoxycephalosporin C synthetase enzyme of  S. clavuligerus  ATCC 27064, or any other protein capable of converting penicillin N into deacetoxycephalosporin C, when produced by a transformed host as claimed in  claim 7 .  
     
     
         13 . The O-carbamoyldesacetylcephalosporin C 7-hydroxylase enzyme of  S. clavuligerus  ATCC-27064, or any other protein capable of converting O-carbamoyldesacetylcephalosporin C into O-carbamoyldesacetyl-7-hydroxycephalosporin C, or cephalosporin C into 7-hydroxycephalosporin C, when produced by a transformed host as claimed in  claim 7 .  
     
     
         14 .  S. clavuligerus  NCIB 12208.  
     
     
         15 . The use of DNA (I) or any fragment thereof capable of hybridising to the DNA of a β-lactam antibiotic producing micro-organism for the purpose of isolating genes involved in β-lactam antibiotic biosynthesis in that organism.