Institute of Food Research, Norwich, NR4 7UA, United Kingdom.
J Biol Chem. 2011 Dec 16;286(50):43301-12. doi: 10.1074/jbc.M111.307835. Epub 2011 Oct 24.
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 ε-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.
完全测序的细菌基因组的可用性表明，许多已知合成多胺亚精胺的物种缺乏 S-腺苷甲硫氨酸脱羧酶和亚精胺合酶的亚精胺生物合成酶。我们发现，这些物种具有sym-norspermidine 生物合成酶 carbo- norspermidine 脱氢酶和 carbo-norspermidine 脱羧酶的同源物。通过在食源性病原体空肠弯曲菌中删除这些基因，我们发现 carbo-norspermidine 脱羧酶同源物负责在体内合成亚精胺而不是 sym-norspermidine。在空肠弯曲菌的多胺营养缺陷基因缺失株中，生长受到高度限制，但可以通过外源性 sym-homospermidine 恢复，在较小程度上也可以通过 sym-norspermidine 恢复。替代的亚精胺生物合成途径存在于许多细菌门中，是人类肠道、胃和口腔微生物组中的主要亚精胺途径，它似乎已经取代了肠道微生物组中的 S-腺苷甲硫氨酸脱羧酶/亚精胺合酶途径。大约一半的肠道Firmicutes 物种似乎是多胺营养缺陷体，但都编码 potABCD 亚精胺/腐胺转运体。在不同的细菌基因组中，与一系列不同的腐胺生物合成基因簇在一起的 carbo-spermidine 脱氢酶和 carbo-spermidine 脱羧酶的同源物编码物，与在亚精胺而不是 sym-norspermidine 生物合成中的作用一致。由于 ε-proteobacteria 在深海热液喷口的普遍性以及替代亚精胺生物合成途径在该门中的普遍性，在深海热液喷口中，carboxyspermidine 途径也是主要的。多胺生物合成的 carbo-spermidine 途径存在于各种人类病原体中，这种替代的亚精胺生物合成途径为开发新型抗菌化合物提供了一个有吸引力的目标。
