Conserved Mechanism of 2'-Phosphorylation-Aided Amide Ligation in Peptidyl Nucleoside Biosynthesis.

ABSTRACT: Peptidyl nucleoside antifungals, represented by nikkomycins and polyoxins, consist of an unusual six-carbon nucleoside [aminohexuronic acid (AHA)] ligated to a nonproteinogenic amino acid via an amide bond. A recent study suggested that AHA is biosynthesized through cryptic phosphorylation, where a 2'-phosphate is introduced early in the pathway and required to form AHA. However, whether 2'-phosphorylation is necessary for the last step of biosynthesis, the formation of the amide bond between AHA and nonproteinogenic amino acids, remains ambiguous. Here, we address this question with comprehensive in vitro and in vivo characterizations of PolG and NikS, which together provide strong evidence that amide ligation proceeds with 2'-phosphorylated substrates in both pathways. Our

SUBMITTER: Draelos MM 

PROVIDER: S-EPMC8415103 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature