Nicotianamine (NA) is a metabolite synthesized by all plants, in which it is involved in the homeostasis of different micronutrients such as iron, nickel or zinc. In some plants it also serves as a precursor of phytosiderophores, which are used for extracellular iron scavenging. Previous studies have also established the presence of NA in filamentous fungi and some mosses, whereas an analogue of NA was inferred in an archaeon. More recently, opine-type metallophores with homology to NA were uncovered in bacteria, especially in human pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa or Yersinia pestis, synthesizing respectively staphylopine, pseudopaline and yersinopine. Here, we review the current state of knowledge regarding the discovery, biosynthesis, function and regulation of these metallophores. We also discuss the genomic environment of the cntL gene, which is homologous to the plant NA synthase (NAS) gene, and plays a central role in the synthesis of NA-like metallophores. This reveals a large diversity of biosynthetic, export and import pathways. Using sequence similarity networks, we uncovered that these metallophores are widespread in numerous bacteria thriving in very different environments, such as those living at the host–pathogen interface, but also in the soil. We additionally established a phylogeny of the NAS/cntL gene and, as a result, we propose that this gene is an ancient gene and NA, or its derivatives, is an ancient metallophore that played a prominent role in metal acquisition or metal resistance. Indeed, our phylogenetic analysis suggests an evolutionary model where the possibility to synthesize this metallophore was present early in the appearance of life, although it was later lost by most living microorganisms, unless facing metal starvation such as at the host–pathogen interface or in some soils. According to our model, NA then re-emerged as a central metabolite for metal homeostasis in fungi, mosses and all known higher plants.

中文翻译：

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烟胺的古老根源：烟胺样金属团的多样性、作用、调控和进化

烟胺 (NA) 是一种由所有植物合成的代谢物，它参与不同微量营养素（如铁、镍或锌）的体内平衡。在一些植物中，它也作为植物铁载体的前体，用于细胞外铁的清除。先前的研究还确定了丝状真菌和一些苔藓中存在 NA，而在古细菌中推断出 NA 的类似物。最近，在细菌中发现了与 NA 同源的 opine 型金属团，尤其是在人类病原体中，如金黄色葡萄球菌、铜绿假单胞菌或鼠疫杆菌，分别合成葡萄碱、假花青素和耶尔西诺平。在这里，我们回顾了关于这些金属团的发现、生物合成、功能和调节的当前知识状态。我们还讨论了cntL基因的基因组环境，该基因与植物 NA 合酶 (NAS) 基因同源，并在 NA 样金属团的合成中起核心作用。这揭示了生物合成、输出和输入途径的多样性。使用序列相似性网络，我们发现这些金属团广泛存在于许多在非常不同的环境中繁衍的细菌中，例如生活在宿主 - 病原体界面的细菌，以及土壤中的细菌。我们另外建立了NAS / cntL的系统发育基因，因此，我们提出该基因是一个古老的基因，而 NA 或其衍生物是一种古老的金属载体，在金属获取或金属抗性中发挥了重要作用。事实上，我们的系统发育分析表明了一种进化模型，其中在生命出现的早期就存在合成这种金属团的可能性，尽管后来大多数活微生物失去了它，除非面临金属饥饿，例如在宿主 - 病原体界面或某些土壤。根据我们的模型，NA 然后作为真菌、苔藓和所有已知高等植物中金属稳态的中心代谢物重新出现。