Bioinformatic Mapping of Opine-Like Zincophore Biosynthesis in Bacteria.
Bioinformatic Mapping of Opine-Like Zincophore Biosynthesis in Bacteria.
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细菌中类松碱锌基团生物合成的生物信息学图谱。
DOI：
10.1128/msystems.00554-20
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发表时间：
2020
期刊：
影响因子：
6.4
通讯作者：
Kehl-Fie,ThomasE
中科院分区：
文献类型：
--
作者：
Morey,JacquelineR;Kehl-Fie,ThomasE
锌是生物系统中必不可少的营养物质，因为它在参与各种细胞过程的蛋白质中需要结构或催化作用。为了满足这种细胞需求，微生物必须从他们的环境中获得足够的锌。然而，许多环境中锌的利用率很低。细菌用来获取锌的机制之一是通过产生被称为锌载体的小分子。与用于铁吸收的细菌铁载体类似，锌载体是由细菌合成的，然后输出，然后作为锌载体-锌络合物重新进口。到目前为止，只有四个锌载体被描述，包括两个来自人类病原体金黄色葡萄球菌和铜绿假单胞菌，它们在感染过程中对锌的获取起关键作用，以及一个在土壤细菌中。为了确定哪些其他微生物可能产生锌载体，我们使用生物信息学分析来识别新的锌载体生物合成基因簇(BGC)，并预测合成分子的多样性。基因组邻域网络分析从放线杆菌、纤毛虫、变形杆菌和梭杆菌中鉴定了大约250种独特的锌细菌产生菌种。这表明锌载体是由栖息在广泛的生态位上的各种细菌产生的。根据与特征化系统的相似性，许多BGC可能产生特征化的锌载体。然而，这一分析也发现了许多BGC，它们基于其他修饰酶的共存和生物合成酶的序列差异，可能产生独特的锌载体。总而言之，这些发现提供了对锌载体生物合成景观的全面了解，这对未来对这些重要小分子的研究将是非常有价值的。重要的是，细菌必须从他们的环境中获得必要的营养，包括锌。对于细菌病原体，这需要克服被称为营养免疫的宿主金属抑制反应。最近在人类病原体金黄色葡萄球菌、铜绿假单胞菌和鼠疫耶尔森菌以及土壤相关细菌粘液拟杆菌中描述了一种新型的锌吸收机制，涉及细菌产生一个小的锌清除分子。这表明锌载体在不同环境中对锌的获取可能是重要的。在这项研究中，我们试图利用生物信息学来鉴定其他产生锌库的细菌。我们鉴定了近250种独特的锌库产生物种，包括人类和动物病原体，以及来自土壤、根际、植物和海洋生境的分离物。至关重要的是，我们观察到了氨基酸和基因组织水平上的多样性，这表明这些物种中的许多正在产生独特的锌载体。总之，我们的发现突显了锌载体对生活在不同环境中的广泛细菌的重要性。
Zinc is an essential nutrient in biological systems due to its structural or catalytic requirement in proteins involved in diverse cellular processes. To meet this cellular demand, microbes must acquire sufficient zinc from their environment. However, many environments have low zinc availability. One of the mechanisms used by bacteria to acquire zinc is through the production of small molecules known as zincophores. Similar to bacterial siderophores used for iron uptake, zincophores are synthesized by the bacterium and exported and then reimported as zincophore-zinc complexes. Thus far, only four zincophores have been described, including two from the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa, in which they play a critical role in zinc acquisition during infection, and one in a soil bacterium. To determine what other microbes may produce zincophores, we used bioinformatic analyses to identify new zincophore biosynthetic gene clusters (BGCs) and predict the diversity of molecules synthesized. Genome neighborhood network analysis identified approximately 250 unique zincophore-producing species from actinobacteria, firmicutes, proteobacteria, and fusobacteria. This indicates that zincophores are produced by diverse bacteria that inhabit a broad range of ecological niches. Many of the BGCs likely produce characterized zincophores, based on similarity to the characterized systems. However, this analysis also identified numerous BGCs that, based on the colocalization of additional modifying enzymes and sequence divergence of the biosynthetic enzymes, are likely to produce unique zincophores. Collectively, these findings provide a comprehensive understanding of the zincophore biosynthetic landscape that will be invaluable for future research on these important small molecules.IMPORTANCEBacteria must acquire essential nutrients, including zinc, from their environment. For bacterial pathogens, this necessitates overcoming the host metal-withholding response known as nutritional immunity. A novel type of zinc uptake mechanism that involves the bacterial production of a small zinc-scavenging molecule was recently described in the human pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Yersinia pestis, as well as the soil-associated bacterium Paenibacillus mucilaginosus. This suggests that zincophores may be important for zinc acquisition in diverse environments. In this study, we sought to identify other zincophore-producing bacteria using bioinformatics. We identified almost 250 unique zincophore-producing species, including human and animal pathogens, as well as isolates from soil, rhizosphere, plant, and marine habitats. Crucially, we observed diversity at the amino acid and gene organization levels, suggesting that many of these species are producing unique zincophores. Together, our findings highlight the importance of zincophores for a broad array of bacteria living in diverse environments.