%0 Journal Article
%T A vitamin K-dependent carboxylase orthologue is involved in antibiotic biosynthesis
%J -
%D 2018
%R https://doi.org/10.1038/s41929-018-0178-2
%X Vitamin K-dependent carboxylase (VKDC) enzymes modify glutamate residues in mammalian vitamin K-dependent proteins, generating ¦Ã-carboxyglutamic acids with malonate moieties that mediate important physiological responses such as blood coagulation. Proteins with sequence similarity to mammalian VKDC are also found in bacteria; however, their function remains unknown. The antibiotic malonomycin from Streptomyces rimosus contains an unusual malonate group, of unknown origin, that is essential for its biological activity. Here, we show that a bacterial VKDC orthologue (MloH) is responsible for the malonic acid moiety in malonomycin. Using CRISPR/Cas9 gene editing, complementation and mutagenesis experiments, this VKDC-like enzyme was shown to ¦Á-carboxylate an aspartyl residue within a hybrid polyketide¨Cnonribosomal peptide intermediate during malonomycin biosynthesis. This study reveals a highly unusual biosynthetic pathway to malonic acid-containing metabolites, providing a functional role for VKDC-like proteins in prokaryotes and a vitamin K-dependent carboxylation reaction with a non-proteinogenic substrate
%U https://www.nature.com/articles/s41929-018-0178-2