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首页> 外文期刊>The Journal of biological chemistry >Alternative Spermidine Biosynthetic Route Is Critical for Growth of Campylobacter jejuni and Is the Dominant Polyamine Pathway in Human Gut Microbiota
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Alternative Spermidine Biosynthetic Route Is Critical for Growth of Campylobacter jejuni and Is the Dominant Polyamine Pathway in Human Gut Microbiota

机译：替代的亚精亚胺生物合成途径对于赤羽弯曲杆菌的生长至关重要，是人体肠道微生物肿瘤中的主要多胺途径

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The availability of fully sequenced bacterial genomes has revealed that many species known to synthesize the polyamine spermidine lack the spermidine biosynthetic enzymes S-adenosylmethionine decarboxylase and spermidine synthase. We found that such species possess orthologues of the sym-norspermidine biosynthetic enzymes carboxynorspermidine dehydrogenase and carboxynorspermidine decarboxylase. By deleting these genes in the food-borne pathogen Campylobacter jejuni, we found that the carboxynorspermidine decarboxylase orthologue is responsible for synthesizing spermidine and not sym-norspermidine in vivo. In polyamine auxotrophic gene deletion strains of C. jejuni, growth is highly compromised but can be restored by exogenous sym-homospermidine and to a lesser extent by sym-norspermidine. The alternative spermidine biosynthetic pathway is present in many bacterial phyla and is the dominant spermidine route in the human gut, stomach, and oral microbiomes, and it appears to have supplanted the S-adenosylmethionine decarboxylase/spermidine synthase pathway in the gut microbiota. Approximately half of the gut Firmicutes species appear to be polyamine auxotrophs, but all encode the potABCD spermidine/putrescine transporter. Orthologues encoding carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase are found clustered with an array of diverse putrescine biosynthetic genes in different bacterial genomes, consistent with a role in spermidine, rather than sym-norspermidine biosynthesis. Due to the pervasiveness of ?-proteobacteria in deep sea hydrothermal vents and to the ubiquity of the alternative spermidine biosynthetic pathway in that phylum, the carboxyspermidine route is also dominant in deep sea hydrothermal vents. The carboxyspermidine pathway for polyamine biosynthesis is found in diverse human pathogens, and this alternative spermidine biosynthetic route presents an attractive target for developing novel antimicrobial compounds.
机译：完全测序的细菌基因组的可用性表明，已知许多已知合成多胺亚胺的物种缺乏硫代胺生物合成酶S-腺苷甲基硫醚脱羧酶和亚精亚胺合成酶。我们发现这些物种具有亚氨基甲酸氨基生物合成酶羧基诺普林宁脱氢酶和羧基诺缬氨酸普赖氨酸脱羧酶的外酯。通过删除食物传播病原体振动杆菌的这些基因，我们发现羧基同学脱羧酶直酯原理是合成亚胺的原因，而不是体内氨氨酰胺。在多胺滋巢营养基因缺失菌株C.Jejuni中，生长受到高度损害，但可以通过外源性羟基吡啶酰胺和较小程度来恢复。替代的亚精亚胺生物合成途径存在于许多细菌植物中，并且是人体肠道，胃和口服微生物胶中的主要硫胺化途径，并且似乎在肠道微生物酵母中似乎将S-腺苷聚甲基硫醚脱羧酶/亚颗粒合成酶途径。大约一半的肠道常规物种似乎是多胺滋巢营养性，但所有这些都是编码POTABCD Femermidine / Putrescine Transporter。发现羧甲酰胺脱氢酶和羧甲酰胺脱羧酶的正晶片与不同的细菌基因组中的各种不同的Putrescine生物合成基因组聚集，与亚精胺的作用一致，而不是Sym-Norspermidine生物合成。由于深海水热通风口中蛋白质的蛋白质蛋白蛋白蛋白，并且在该门的替代亚精肽生物合成途径中，羧甲酰丙烯酸铅也占据了深海水热通风口中。多胺生物合成的羧甲酰胺途径在不同的人类病原体中发现，并且这种替代的亚精胺生物合成途径具有开发新型抗微生物化合物的有吸引力的靶标。

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