Abstract
Metal homeostasis poses a major challenge to microbes, which must acquire
scarce elements for core metabolic processes. Methanobactin, an extensively modified
copper-chelating peptide, was one of the earliest natural products shown to enable
microbial acquisition of a metal other than iron. We describe the core biosynthetic
machinery responsible for the characteristic posttranslational modifications that grant
methanobactin its specificity and affinity for copper. A heterodimer comprising MbnB, a
DUF692 family iron enzyme, and MbnC, a protein from a previously unknown family, performs
a dioxygen-dependent four-electron oxidation of the precursor peptide (MbnA) to install an
oxazolone and an adjacent thioamide, the characteristic methanobactin bidentate copper
ligands. MbnB and MbnC homologs are encoded together and separately in many bacterial
genomes, suggesting functions beyond their roles in methanobactin biosynthesis