甲烷氧化菌素研究进展

Advances in methanobactin

甲烷氧化菌素(methanobactin,Mbn)最早发现于甲烷氧化菌,是一类由核糖体合成的翻译后修饰肽,其特征是特定的半胱氨酸残基被修饰成恶唑酮-硫代酰胺基团.Mbn对铜离子具有高度亲和性,在甲烷氧化菌的铜稳态生理调控中发挥了重要的作用.近年,在其他种属的细菌中也发现了Mbn操纵子的存在,并根据系统发育分析将其分为五大类(groupsⅠ–Ⅴ).目前已经分离鉴定的Mbn既有结构的保守性,也有序列的特异性.除了铜螯合特性,Mbn还被证明具有氧化酶活性、解汞毒能力以及抑菌作用等,尤其在治疗铜代谢相关疾病、细菌感染性疾病等方面具有潜在的开发价值.本文对Mbn的种类、结构、生物合成机制和生物学功能等方面的研究成果进行综述,并展望其应用前景,旨在为Mbn的开发应用提供理论指导和科学支撑.

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,mbn A,mbn B and mbn C,as well as the composition and arrangement of adjacent genes,researchers have divided the Mbn operons into five groups(GroupsⅠ–Ⅴ).In addition,some species contain several different types of Mbn simultaneously.Mbn A is a precursor peptide of Mbn and is composed of an N-terminal lead peptide(LP)and a C-terminal core peptide(CP);Mbn B is an iron-containing enzyme that directly participates in the posttranslational modification of Mbn A;Mbn C is mainly involved in the recognition and binding of Mbn A.Mbn B and Mbn C 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 Mbn A CP.The LP of modified Mbn A 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 Ms Mbn 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.