Departments of Molecular Biosciences and of Chemistry, Northwestern University, Evanston, IL 60208, USA.
BMC Biol. 2013 Feb 26;11:17. doi: 10.1186/1741-7007-11-17.
Methanobactins (Mbns) are a family of copper-binding natural products involved in copper uptake by methanotrophic bacteria. The few Mbns that have been structurally characterized feature copper coordination by two nitrogen-containing heterocycles next to thioamide groups embedded in a peptidic backbone of varying composition. Mbns are proposed to derive from post-translational modification of ribosomally synthesized peptides, but only a few genes encoding potential precursor peptides have been identified. Moreover, the relevance of neighboring genes in these genomes has been unclear.
The potential for Mbn production in a wider range of bacterial species was assessed by mining microbial genomes. Operons encoding Mbn-like precursor peptides, MbnAs, were identified in 16 new species, including both methanotrophs and, surprisingly, non-methanotrophs. Along with MbnA, the core of the operon is formed by two putative biosynthetic genes denoted MbnB and MbnC. The species can be divided into five groups on the basis of their MbnA and MbnB sequences and their operon compositions. Additional biosynthetic proteins, including aminotransferases, sulfotransferases and flavin adenine dinucleotide (FAD)-dependent oxidoreductases were also identified in some families. Beyond biosynthetic machinery, a conserved set of transporters was identified, including MATE multidrug exporters and TonB-dependent transporters. Additional proteins of interest include a di-heme cytochrome c peroxidase and a partner protein, the roles of which remain a mystery.
This study indicates that Mbn-like compounds may be more widespread than previously thought, but are not present in all methanotrophs. This distribution of species suggests a broader role in metal homeostasis. These data provide a link between precursor peptide sequence and Mbn structure, facilitating predictions of new Mbn structures and supporting a post-translational modification biosynthetic pathway. In addition, testable models for Mbn transport and for methanotrophic copper regulation have emerged. Given the unusual modifications observed in Mbns characterized thus far, understanding the roles of the putative biosynthetic proteins is likely to reveal novel pathways and chemistry.
甲烷菌素（Mbn）是一类参与甲烷氧化菌铜摄取的铜结合天然产物。少数结构特征明确的 Mbn 具有由紧邻硫酰胺基团的两个含氮杂环提供的铜配位，嵌入不同组成的肽骨架中。Mbn 被认为来源于核糖体合成肽的翻译后修饰，但仅鉴定出少数编码潜在前体肽的基因。此外，这些基因组中相邻基因的相关性尚不清楚。
通过挖掘微生物基因组，评估了更广泛的细菌物种产生 Mbn 的潜力。在 16 个新物种中鉴定出编码 Mbn 样前体肽（MbnA）的操纵子，包括甲烷氧化菌和令人惊讶的非甲烷氧化菌。与 MbnA 一起，操纵子的核心由两个假定的生物合成基因 MbnB 和 MbnC 组成。根据 MbnA 和 MbnB 序列及其操纵子组成，可将这些物种分为五个组。在一些家族中还鉴定出其他生物合成蛋白，包括氨基转移酶、磺基转移酶和黄素腺嘌呤二核苷酸（FAD）依赖性氧化还原酶。除生物合成机制外，还鉴定出了一组保守的转运蛋白，包括 MATE 多药外排泵和 TonB 依赖性转运蛋白。其他感兴趣的蛋白质包括二血红细胞色素 c 过氧化物酶和一个伴侣蛋白，其作用仍然是个谜。
本研究表明，Mbn 类似化合物的分布可能比以前认为的更为广泛，但并非所有甲烷氧化菌都存在。这种物种分布表明其在金属稳态中具有更广泛的作用。这些数据将前体肽序列与 Mbn 结构联系起来，有利于预测新的 Mbn 结构，并支持翻译后修饰生物合成途径。此外，已经出现了 Mbn 转运和甲烷氧化菌铜调节的可测试模型。鉴于迄今为止所描述的 Mbns 中观察到的异常修饰，了解假定生物合成蛋白的作用可能揭示新的途径和化学。
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