Disease relevance of Clavaminic acid

• Purification and characterization of clavaminate synthase from Streptomyces antibioticus. A multifunctional enzyme of clavam biosynthesis [1].

High impact information on Clavaminic acid

• Expression and purification of two isozymes of clavaminate synthase and initial characterization of the iron binding site. General error analysis in polymerase chain reaction amplification [2].
• Genes specific for the biosynthesis of clavam metabolites antipodal to clavulanic acid are clustered with the gene for clavaminate synthase 1 in Streptomyces clavuligerus [3].
• Portions of the Streptomyces clavuligerus chromosome flanking cas1, which encodes the clavaminate synthase 1 isoenzyme (CAS1), have been cloned and sequenced [3].
• CS catalyzes the oxidative cyclization/desaturation of proclavaminic acid to clavaminic acid in a two-step process involving the intermediacy of dihydroclavaminic acid [Salowe, S. P., Krol, W. J., Iwata-Reuyl, D., & Townsend, C. A. (1991) Biochemistry 30, 2281-2292] [4].
• Mutagenesis studies on the iron binding ligands of clavaminic acid synthase [5].

Chemical compound and disease context of Clavaminic acid

• Two isozymes of clavaminate synthase central to clavulanic acid formation: cloning and sequencing of both genes from Streptomyces clavuligerus [4].

Biological context of Clavaminic acid

• ORFs encoded within the region included ones with similarity to beta-lactam synthase and clavaminic acid synthase, as well as amino acid synthesis enzymes [6].

Associations of Clavaminic acid with other chemical compounds

• Site-directed mutagenesis and biochemical analysis of the endogenous ligands in the ferrous active site of clavaminate synthase. The His-3 variant of the 2-His-1-carboxylate model [7].
• Mutagenesis of the four cysteines and a glutamine residue, conserved in both clavaminic acid synthase isozymes 1 and 2, demonstrated that none of these residues is essential for activity [5].
• Mutagenesis studies on conserved histidine residues identified as possible metal binding ligands in clavaminic acid synthase isozyme 2 were consistent with His-145 and His-280 acting as iron ligands, in support of crystallographic and previous mutagenesis studies [5].

References