Phosphorylation of peptides by a kinase domain in cyanobactin pathways.

ABSTRACT: Phosphorylation is an important protein post-translational modification and a valuable tool in medicinal chemistry for improving the pharmacological properties of small molecules, but rare in natural product biosynthesis. Here we report phosphorylation in cyanobactins, a family of ribosomally synthesized and post-translationally modified peptides. We identify an unusual kinase domain embedded in the C-terminal macrocyclase encoded in cyanobactin biosynthetic gene clusters and link it to the production of phosphorylated dolichospermamides and aphanizomenamides. Heterologous expression, domain deletion and site directed mutagenesis confirm the role of the kinase domain, while transplantation of this domain into the sphaerocyclamide pathway leads to the production of phosphorylated sphaerocyc

SUBMITTER: Castelo-Branco R 

PROVIDER: S-EPMC12639078 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature