Comparative Genomics and Metabolomics Analyses of Clavulanic Acid-Producing Species Provides Insight Into Specialized Metabolism.

Clavulanic acid is a bacterial specialized metabolite, which inhibits certain serine β-lactamases, enzymes that inactivate β-lactam antibiotics to confer resistance. Due to this activity, clavulanic acid is widely used in combination with penicillin and cephalosporin (β-lactam) antibiotics to treat infections caused by β-lactamase-producing bacteria. Clavulanic acid is industrially produced by fermenting , as large-scale chemical synthesis is not commercially feasible.

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

In Streptomyces clavuligerus, the gene cluster involved in the biosynthesis of the clinically used β-lactamase inhibitor clavulanic acid contains a gene (orf12 or cpe) encoding a protein with a C-terminal class A β-lactamase-like domain. The cpe gene is essential for clavulanic acid production, and the recent crystal structure of its product (Cpe) was shown to also contain an N-terminal isomerase/cyclase-like domain, but the function of the protein remains unknown. In the current study, we show that Cpe is a cytoplasmic protein and that both its N- and C-terminal domains are required for in vivo clavulanic acid production in S.

Mycobacterial Membrane Proteins QcrB and AtpE: Roles in Energetics, Antibiotic Targets, and Associated Mechanisms of Resistance.

Infections caused by mycobacteria are difficult to treat due to their inherent physiology, cellular structure, and intracellular lifestyle. Mycobacterium tuberculosis is a pathogen of global concern as it causes tuberculosis (TB) in humans, which requires 6-9 months of chemotherapy. The situation is further exacerbated in the case of infections caused by drug-resistant strains, which necessitate the prolonged use of agents associated with increased host toxicities.