National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland, USA.
BMC Genomics. 2022 Mar 5;23(1):182. doi: 10.1186/s12864-022-08426-7.
Equol, an isoflavonoid metabolite with possible health benefits in humans, is known to be produced by some human gut bacteria. While the genes encoding the equol production pathway have been characterized in a few bacterial strains, a systematic analysis of the equol production pathway is currently lacking.
This study presents an analysis of the taxonomic distribution and evolutionary history of the gene cluster encoding the equol production pathway. A survey for equol gene clusters within the Genome Taxonomy Database bacterial genomes and human gut metagenomes resulted in the identification of a highly conserved gene cluster found in nine bacterial species from the Eggerthellaceae family. The identified gene clusters from human gut metagenomes revealed potential variations in the equol gene cluster organization and gene content within the equol-producing Eggerthellaceae clades. Subsequent analysis showed that in addition to the four genes directly involved in equol production, multiple other genes were consistently found in the equol gene clusters. These genes were predicted to encode a putative electron transport complex and hydrogenase maturase system, suggesting potential roles for them in the equol production pathway. Analysis of the gene clusters and a phylogenetic reconstruction of a putative NAD kinase gene provided evidence of the recent transfer of the equol gene cluster from a basal Eggerthellaceae species to Slackia_A equolifaciens, Enteroscipio sp000270285, and Lactococcus garvieae 20-92.
This analysis demonstrates that the highly conserved equol gene cluster is taxonomically restricted to the Eggerthellaceae family of bacteria and provides evidence of the role of horizontal gene transfer in the evolutionary history of these genes. These results provide a foundation for future studies of equol production in the human gut and future efforts related to bioengineering and the use of equol-producing bacteria as probiotics.
黄豆苷元是一种具有潜在健康益处的异黄酮代谢物，已知可由一些人类肠道细菌产生。虽然编码黄豆苷元生产途径的基因已在少数几种细菌菌株中得到了描述，但目前还缺乏对黄豆苷元生产途径的系统分析。
本研究分析了编码黄豆苷元生产途径的基因簇的分类分布和进化历史。在基因组分类数据库细菌基因组和人类肠道宏基因组中对黄豆苷元基因簇进行调查，结果在 Eggerthellaceae 科的 9 个细菌种中发现了一个高度保守的基因簇。从人类肠道宏基因组中鉴定出的基因簇揭示了黄豆苷元产生的 Eggerthellaceae 进化枝中基因簇组织和基因内容的潜在变化。随后的分析表明，除了直接参与黄豆苷元生产的四个基因外，在黄豆苷元基因簇中还发现了多个其他基因。这些基因预测编码一个假定的电子传递复合物和氢化酶成熟酶系统，表明它们在黄豆苷元生产途径中可能具有潜在作用。对基因簇的分析和一个假定的 NAD 激酶基因的系统发育重建提供了证据，证明了黄豆苷元基因簇是从一个基础 Eggerthellaceae 种到 Slackia_A equolifaciens、Enteroscipio sp000270285 和 Lactococcus garvieae 20-92 的最近水平基因转移而来的。
本分析表明，高度保守的黄豆苷元基因簇在分类上仅限于 Eggerthellaceae 科的细菌，并提供了水平基因转移在这些基因进化历史中的作用的证据。这些结果为未来在人类肠道中进行黄豆苷元生产的研究以及与生物工程和使用黄豆苷元产生细菌作为益生菌相关的未来努力提供了基础。
