FIG 7.

Integration of pks and HPI expression regulation into the Csr- and Fur-dependent regulatory networks. Colibactin and yersiniabactin expression both respond to central carbon- and iron-dependent regulation. CsrA inhibits at the posttranscriptional level expression of several genes of the colibactin and high pathogenicity island. The ferric uptake regulator (Fur) inhibits transcription of clbA, but also of ybtA and fyuA. The small regulatory noncoding RNA ryhB inhibits clbA expression at the posttranscriptional level. The ryhB regulatory RNA also modulates the efficiency of nonribosomal peptide biosynthesis via channeling of serine as a building block into colibactin and yersiniabactin biosynthesis (dashed arrow). Furthermore, the phosphopantetheinyl transferase ClbA activates polyketide synthases and nonribosomal peptide synthetases of both the colibactin as well as the yersiniabactin biosynthesis machinery.