Discovery of a Two-Step Enzyme Cascade Converting Aspartate to Aminomalonate in Peptide Natural Product Biosynthesis.

ABSTRACT: Aminomalonic acid (Ama) is found in various natural products and protein hydrolysates of multiple organisms, but the understanding of its biosynthetic origin remains largely limited. By exploiting a biosynthetic gene cluster for ribosomally synthesized and post-translationally modified peptides (RiPPs), which are rich sources of new enzyme chemistry, we identified a novel two-enzyme pathway for Ama biosynthesis. This biosynthetic pathway, mediated by an Fe(II)/2-oxoglutarate-dependent oxygenase (Fe(II)/2OG), SmaO, and an atypical Fe(II)-dependent histidine-aspartate (HD) domain enzyme, SmaX, converts aspartate (Asp) to β-hydroxyaspartic acid (Hya) intermediate and ultimately to Ama. These tandem enzymatic reactions─hydroxylation of the carbon next to an acid functional group and subsequent

SUBMITTER: Kim HW 

PROVIDER: S-EPMC12186529 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature