Clavulanic acid dehydrogenase: structural and biochemical analysis of the final step in the biosynthesis of the beta-lactamase inhibitor clavulanic acid.

  title={Clavulanic acid dehydrogenase: structural and biochemical analysis of the final step in the biosynthesis of the beta-lactamase inhibitor clavulanic acid.},
  author={Alasdair K Mackenzie and Nadia J Kershaw and Helena Hernández and Carol V. Robinson and Christopher J. Schofield and Inger Andersson},
  volume={46 6},
The ultimate step in the biosynthesis of the medicinally important beta-lactamase inhibitor clavulanic acid is catalyzed by clavulanic acid dehydrogenase (CAD). CAD is responsible for the NAPDH-dependent reduction of the unstable intermediate clavulanate-9-aldehyde to yield clavulanic acid. Here, we report biochemical and structural studies on CAD. Biophysical analyses demonstrate that CAD exists as dimeric and tetrameric species in solution. The reaction performed by CAD was shown to be… 

In vivo functional analysis of a class A β-lactamase-related protein essential for clavulanic acid biosynthesis in Streptomyces clavuligerus

The suggested in vivo involvement of an isomerase-like domain recruited by an ancestral β-lactamase related protein, supports a previous hypothesis that Cpe could be involved in a step requiring the opening and modification of the clavulanic acid core during its biosynthesis from 5S precursors.

Crystal structure of serine dehydrogenase from Escherichia coli: important role of the C-terminal region for closed-complex formation.

It is revealed that the C-terminal region possesses the important roles in substrate binding through the stabilization of the substrate-binding loop in the closed form complex.

Biochemical and structural investigation of sulfoacetaldehyde reductase from Klebsiella oxytoca.

Biochemical investigations of the substrate scope of IsfD, and bioinformatics analysis of IsFD homologs, suggest that Isf D is related to the promiscuous 3-hydroxyacid dehydrogenases with diverse metabolic functions.

Structural and functional analysis of angucycline C-6 ketoreductase LanV involved in landomycin biosynthesis.

Determination of the structure of LanV in complex with 11-deoxylandomycinone at 2.0 Å resolution indicated that substrate binding does not induce large conformational changes and that substrate recognition occurs mainly through hydrophobic interactions, and a coordinated water molecule was confirmed to be critical for the catalytic activity by site-directed mutagenesis.

Clavulanic acid biosynthesis and genetic manipulation for its overproduction

In this review, clavulanic acid biosynthesis and the associated gene clusters are discussed, and clavuranic acid improvement through genetic manipulation is explained.

Crystallographic and mass spectrometric analyses of a tandem GNAT protein from the clavulanic acid biosynthesis pathway

Crystallographic and mass spectrometric evidence suggests that binding of the second acyl‐CoA occurs preferentially to monomeric rather than dimeric CBG, and analysis of the CBG structures, together with those of other tandem GNAT proteins, suggest that the AcCoA in the N‐terminal GNAT domain plays a structural role whereas the C‐Terminal domain is more likely to be directly involved in acetyl transfer.

A comparison of the clavam biosynthetic gene clusters in Streptomyces antibioticus Tü1718 and Streptomyces clavuligerus.

A potential clavam biosynthetic pathway consistent with the genes in the cluster and the metabolites produced by S. antibioticus, and correspondingly different from that of S. clavuligerus, is proposed.