clbQ

ClbQ is a gene within the colibactin biosynthetic gene cluster (clbA–clbS) found in several pathogenic strains of Escherichia coli. It encodes a type II thioesterase that functions as an editing enzyme during colibactin assembly, hydrolyzing misprimed or stalled thioester intermediates on carrier protein domains and thereby facilitating turnover and product formation.

Genetic inactivation of clbQ often reduces the yield of colibactin-related metabolites and attenuates genotoxic activity in functional assays, supporting a role in biosynthesis rather than direct steps of final toxin construction. The exact substrate range is not fully defined; candidates include aberrant acyl or aminoacyl thioesters tethered to ACP- or PCP-like domains within the pathway.

Biochemical and structural analyses place ClbQ in the TEII family with an alpha/beta hydrolase–like fold. Active-site residues around a catalytic serine support hydrolysis of thioester bonds. By removing stalled intermediates, ClbQ is thought to promote productive offloading or recycling of intermediates, reducing derailed steps in the pathway.

ClbQ’s expression is coordinated with the rest of the clb cluster, which is regulated by environmental signals and linked to pathogenicity through colibactin production. Ongoing research aims to define its precise substrate scope and interactions with other colibactin biosynthetic enzymes.