clbA

clbA is a gene encoding a phosphopantetheinyl transferase (PPTase) that is part of the colibactin biosynthetic gene cluster (the pks island) found in certain Escherichia coli strains. The pks island encodes the enzymatic machinery responsible for the production of colibactin, a hybrid polyketide-nonribosomal peptide metabolite implicated as a genotoxin.

The ClbA protein belongs to the Sfp-type PPTase family and functions by transferring a 4'-phosphopantetheine moiety from coenzyme A to specific serine residues on carrier proteins within the colibactin assembly line. This post-translational modification converts inactive apo-carrier proteins into active holo-carrier proteins, enabling the proper operation of the polyketide synthase and nonribosomal peptide synthetase modules that build colibactin. In this way, ClbA is essential for the activation steps that drive colibactin biosynthesis.

Genetic studies show that disrupting clbA abolishes colibactin production and markedly reduces, or eliminates, the associated genotoxic effects on host cells in vitro. In strains carrying the pks island, ClbA can act on multiple carrier proteins, supporting the modular assembly of colibactin. The presence of the pks island, including clbA, has been associated with DNA damage in experimental models and has been investigated for potential links to colorectal cancer risk in humans, though the precise contribution to disease remains under active study.

ClbA is typically co-located with other pks island genes and is found in a subset of pathogenic and some commensal E. coli lineages. Understanding ClbA's function helps clarify how colibactin biosynthesis is regulated and how bacterial genotoxins may influence host–microbe interactions.