Advances in methanobactin

Methanobactins (Mbns), first discovered in methanotrophs, constitute a class of ribosomally synthesized and posttranslationally modified peptides characterized by specific cysteine residues modified with oxazolone-thioamide moieties. Mbns have a high affinity for copper and play an important role in copper homeostasis in methanogenic bacteria. With continued research, an increasing number of Mbns have been isolated and identified. In recent years, Mbn operons have also been found in a much wider range of bacteria. According to phylogenetic analysis of the core components of the operon, mbnA, mbnB and mbnC, as well as the composition and arrangement of adjacent genes, researchers have divided the Mbn operons into five groups (Groups I-V). In addition, some species contain several different types of Mbn simultaneously. MbnA is a precursor peptide of Mbn and is composed of an N-terminal lead peptide (LP) and a C-terminal core peptide (CP); MbnB is an iron-containing enzyme that directly participates in the posttranslational modification of MbnA; MbnC is mainly involved in the recognition and binding of MbnA. MbnB and MbnC are assembled into an Mbn core protein machine that is responsible for the generation of oxazolone-thioamide moieties on the cysteine and its adjacent residues on the MbnA CP. The LP of modified MbnA is excised and becomes a biologically active Mbn. However, the removal mechanism is not clear. To date, researchers have isolated and identified nearly ten kinds of Mbns from the fermentation broth of methanotrophs. These Mbns are structurally conserved, but there is limited sequence conservation, and all contain oxazolone-thioamide moieties that interact with copper ions. At present, the most well studied Mbn is MsMbn from the methanotroph Methylosinus (Ms) trichosporium OB3b, which is secreted to bind copper ions in the environment when the bacterium is deficient in copper and then to transport the copper to the bacterium in the form of a Mbn-Cu complex to regulate copper homeostasis. In addition to participating in the regulation of bacterial copper homeostasis, Mbn also has various other functional activities. For example, the Mbn-Cu complex has been proven to have oxidase, superoxide dismutase and hydrogen peroxide reductase activities. Some studies have shown that Mbn also has the ability to chelate heavy metals such as mercury and gold, which may have use in ecological environment management applications. Moreover, it also has a growth inhibition effect on some gram-positive bacteria, indicating that it has potential to be developed as a clinical antibacterial drug. At the same time, some preclinical studies have shown that it can be applied to treat clinical diseases caused by metal ion disorders, such as Wilson's disease (WD). This paper reviews the species, structures, biosynthesis and biological functions of Mbn and proposes applications, aiming to provide theoretical guidance and scientific support for the development and application of Mbn.