Controlling Megasynthetase Module-Module Interactions through β-Hairpin Docking Domain Engineering.

ABSTRACT: Bacteria manufacture a diversity of natural products with pharmaceutical value, many from modular polyketide synthase (PKS), nonribosomal peptide synthetase (NRPS), or hybrid pathways. In these pathways, each module extends a biosynthetic intermediate by an acyl unit (PKS) or amino acid (NRPS), employing a carrier domain (CP) to deliver the pathway intermediate to successive active sites and to the subsequent module. Docking domains (DD) at polypeptide termini ensure pathway fidelity by specific noncovalent association of sequential modules. The vatiamide biosynthetic gene cluster encodes a rare trifurcated pathway, enabled by a short linear motif (SLiM) at the C-terminus of VatM that docks with identical β-hairpin domains (βHDs) at the N-termini of VatN, VatQ, and VatS. Taking inspiration

SUBMITTER: Rankin MR 

PROVIDER: S-EPMC12831602 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature