Title : Genes specific for the biosynthesis of clavam metabolites antipodal to clavulanic acid are clustered with the gene for clavaminate synthase 1 in Streptomyces clavuligerus - Mosher_1999_Antimicrob.Agents.Chemother_43_1215 |
Author(s) : Mosher RH , Paradkar AS , Anders C , Barton B , Jensen SE |
Ref : Antimicrobial Agents & Chemotherapy , 43 :1215 , 1999 |
Abstract :
Portions of the Streptomyces clavuligerus chromosome flanking cas1, which encodes the clavaminate synthase 1 isoenzyme (CAS1), have been cloned and sequenced. Mutants of S. clavuligerus disrupted in cvm1, the open reading frame located immediately upstream of cas1, were constructed by a gene replacement procedure. Similar techniques were used to generate S. clavuligerus mutants carrying a deletion that encompassed portions of the two open reading frames, cvm4 and cvm5, located directly downstream of cas1. Both classes of mutants still produced clavulanic acid and cephamycin C but lost the ability to synthesize the antipodal clavam metabolites clavam-2-carboxylate, 2-hydroxymethyl-clavam, and 2-alanylclavam. These results suggested that cas1 is clustered with genes essential and specific for clavam metabolite biosynthesis. When a cas1 mutant of S. clavuligerus was constructed by gene replacement, it produced lower levels of both clavulanic acid and most of the antipodal clavams except for 2-alanylclavam. However, a double mutant of S. clavuligerus disrupted in both cas1 and cas2 produced neither clavulanic acid nor any of the antipodal clavams, including 2-alanylclavam. This outcome was consistent with the contribution of both CAS1 and CAS2 to a common pool of clavaminic acid that is shunted toward clavulanic acid and clavam metabolite biosynthesis. |
PubMedSearch : Mosher_1999_Antimicrob.Agents.Chemother_43_1215 |
PubMedID: 10223939 |
Gene_locus related to this paper: strcl-a0pcj7 , strcl-CVM4 |
Gene_locus | strcl-a0pcj7 strcl-CVM4 |
Mosher RH, Paradkar AS, Anders C, Barton B, Jensen SE (1999)
Genes specific for the biosynthesis of clavam metabolites antipodal to clavulanic acid are clustered with the gene for clavaminate synthase 1 in Streptomyces clavuligerus
Antimicrobial Agents & Chemotherapy
43 :1215
Mosher RH, Paradkar AS, Anders C, Barton B, Jensen SE (1999)
Antimicrobial Agents & Chemotherapy
43 :1215