Structure Prediction and Genome Mining-Aided Discovery of the Bacterial C-Terminal Tryptophan Prenyltransferase PalQ

Post-translational prenylations, found in eukaryotic primary metabolites and bacterial secondary metabolites, play crucial roles in biomolecular interactions. Employing genome mining methods combined with AlphaFold2-based predictions of protein interactions, PalQ , a prenyltransferase responsible for the tryptophan prenylation of RiPPs produced by Paenibacillus alvei, is identified. PalQ differs from cyanobactin prenyltransferases because of its evolutionary relationship to isoprene synthases, which enables PalQ to transfer extended prenyl chains to the indole C3 position. This prenylation introduces structural diversity to the tryptophan side chain and also leads to conformational dynamics in the peptide backbone, attributed to the cis/trans isomerization that arises from the formation of a pyrrolidine ring. Additionally, PalQ exhibited pronounced positional selectivity for the C-terminal tryptophan. Such enzymatic characteristics offer a toolkit for peptide therapeutic lipidation. Tryptophan prenyltransferase PalQ is a novel member of the isoprene synthase domain superfamily. The C3 prenylation of the tryptophan side chain, mediated by PalQ, alters the conformational dynamics of the peptide backbone.image

Automated summary

Post-translational prenylations play crucial roles in biomolecular interactions. The prenyltransferase PalQ was identified, which can transfer extended prenyl chains to the indole C3 position. This prenylation introduces structural diversity to the tryptophan side chain and alters the conformational dynamics of the peptide backbone.