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Computational genomic discovery of diverse gene clusters harbouring Fe-S flavoenzymes in anaerobic gut microbiota.
Microbial Genomics ( IF 3.9 ) Pub Date : 2020-05-12 , DOI: 10.1099/mgen.0.000373
Victòria Pascal Andreu 1 , Michael A Fischbach 2 , Marnix H Medema 1
Affiliation  

The gut contains an enormous diversity of simple as well as complex molecules from highly diverse food sources, together with host-secreted molecules. This presents a large metabolic opportunity for the gut microbiota, but little is known about how gut microbes are able to catabolize this large chemical diversity. Recently, Fe-S flavoenzymes were found to be key in the transformation of bile acids, catalysing the key step in the 7α-dehydroxylation pathway that allows gut bacteria to transform cholic acid into deoxycholic acid, an exclusively microbe-derived molecule with major implications for human health. While this enzyme family has also been implicated in a limited number of other catalytic transformations, little is known about the extent to which it is of more global importance in gut microbial metabolism. Here, we perform a large-scale computational genomic analysis to show that this enzyme superfamily has undergone a remarkable expansion in Clostridiales, and occurs throughout a diverse array of >1000 different families of putative metabolic gene clusters. Analysis of the enzyme content of these gene clusters suggests that they encode pathways with a wide range of predicted substrate classes, including saccharides, amino acids/peptides and lipids. Altogether, these results indicate a potentially important role of this protein superfamily in the human gut, and our dataset provides significant opportunities for the discovery of novel pathways that may have significant effects on human health.

中文翻译:

计算基因组学发现厌氧肠道菌群中含有Fe-S黄素酶的各种基因簇。

肠道含有来自高度多样化食物来源的简单分子和复杂分子,以及宿主分泌的分子。这为肠道菌群提供了巨大的代谢机会,但对肠道菌种如何能够分解这种化学多样性的知之甚少。最近,发现Fe-S黄素酶是胆汁酸转化的关键,它催化了7α-脱羟基途径的关键步骤,使肠道细菌将胆酸转化为脱氧胆酸,这是微生物的唯一分子,对人类健康。尽管该酶家族也参与了有限数量的其他催化转化,但人们对其在肠道微生物代谢中更重要的程度还知之甚少。这里,我们进行了大规模的计算基因组分析,结果表明该酶超家族在梭菌中经历了显着扩展,并在超过1000个不同家族的推定代谢基因簇中广泛分布。对这些基因簇的酶含量的分析表明,它们编码的途径具有广泛的预测底物种类,包括糖,氨基酸/肽和脂质。总而言之,这些结果表明该蛋白质超家族在人类肠道中的潜在重要作用,我们的数据集为发现可能对人类健康产生重大影响的新途径提供了重要机会。1000个不同家族的推定代谢基因簇。对这些基因簇的酶含量的分析表明,它们编码的途径具有广泛的预测底物种类,包括糖,氨基酸/肽和脂质。总而言之,这些结果表明该蛋白质超家族在人类肠道中的潜在重要作用,我们的数据集为发现可能对人类健康产生重大影响的新途径提供了重要机会。1000个不同家族的推定代谢基因簇。对这些基因簇的酶含量的分析表明,它们编码的途径具有广泛的预测底物种类,包括糖,氨基酸/肽和脂质。总而言之,这些结果表明该蛋白质超家族在人类肠道中的潜在重要作用,我们的数据集为发现可能对人类健康产生重大影响的新途径提供了重要机会。
更新日期:2020-05-14
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