Intestinal microbiota as a tetrahydrobiopterin exogenous source in hph-1 mice
Intestinal microbiota as a tetrahydrobiopterin exogenous source in hph-1 mice
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DOI：
10.1038/srep39854
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发表时间：
2017-01-12
影响因子：
4.6
通讯作者：
Allen-Vercoe, Emma
中科院分区：
文献类型：
--
作者：
Belik, Jaques;Shifrin, Yulia;Allen-Vercoe, Emma
四氢生物蝶呤（BH4）是许多调节酶的辅助因子。虽然没有已知的BH4外源性来源，但在GTP环水解酶1缺陷型高苯丙氨酸血症-1 （hph-1）小鼠中，这种生物terin的组织含量随着年龄的增长而增加。由于已知某些细菌会产生BH4，我们假设肠道微生物群产生这种生物terin有助于hph-1成年小鼠的组织增加。本研究的目的是比较评估hph-1小鼠和野生型C57Bl/6对照组肠道中产生bh4的细菌的存在。在新生和成年小鼠粪便中筛选6-丙酮酰四氢蝶呤合成酶（PTPS-2），这种酶仅存在于产生bh4的细菌中。成年而非新生小鼠、野生型对照和hph-1小鼠粪便中含有PTPS-2 mRNA，表明存在产生bh4的细菌。利用抑化菌培养的人类粪便细菌，我们鉴定出产生ptps -2的细菌属于放线菌门。我们进一步证实，至少有两种产生ptps -2的物种，相等革氏阿尔德克氏菌和施莱氏微杆菌，产生BH4，并存在于hph-1粪便中。综上所述，肠道放线菌产生BH4。这一发现具有重要的翻译意义，因为对先天性生物蝶呤缺乏症患者肠道菌群的控制可能会增加体内BH4的含量。
Tetrahydrobiopterin (BH4) is a cofactor of a number of regulatory enzymes. Although there are no known BH4 exogenous sources, the tissue content of this biopterin increases with age in GTP cyclohydrolase 1-deficient hyperphenylalaninemia-1 (hph-1) mice. Since certain bacteria are known to generate BH4, we hypothesize that generation of this biopterin by the intestinal microbiota contributes to its tissue increase in hph-1 adult mice. The goal of this study was to comparatively evaluate hph-1 mice and wild-type C57Bl/6 controls for the presence of intestinal BH4-producing bacteria. Newborn and adult mice fecal material was screened for 6-pyruvoyltetrahydropterin synthase (PTPS-2) an enzyme only present in BH4-generating bacteria. Adult, but not newborn, wild-type control and hph-1 mouse fecal material contained PTPS-2 mRNA indicative of the presence of BH4-generating bacteria. Utilizing chemostat-cultured human fecal bacteria, we identified the PTPS-2-producing bacteria as belonging to the Actinobacteria phylum. We further confirmed that at least two PTPS-2-producing species, Aldercreutzia equolifaciens and Microbacterium schleiferi, generate BH4 and are present in hph-1 fecal material. In conclusion, intestinal Actinobacteria generate BH4. This finding has important translational significance, since manipulation of the intestinal flora in individuals with congenital biopterin deficiency may allow for an increase in total body BH4 content.