Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; College of Pharmacy, Dalian Medical University, Dalian 116044, China.
College of Pharmacy, Dalian Medical University, Dalian 116044, China.
J Hazard Mater. 2024 Jan 5;461:132617. doi: 10.1016/j.jhazmat.2023.132617. Epub 2023 Sep 22.
Environmental hormones have attracted more attention because of their adverse impact on the health and ecological security of human. Biodegradation is still an efficient tactics to remove environmental hormones, but human intestinal microbes remain to be elucidated in the role of their degradation. In the present work, we intended to perform the in vitro experiment for investigating the degradation of 17β-estradiol, the main environmental estrogen, by human intestinal microflora Aspergillus niger RG13B1. Its degradation led to the production of eighteen metabolites characterized by H, C, and 2D NMR, and HRMS spectra, including nine new (1-9) and nine known metabolites (10-18). Based on their structures, the degradation pathway of 17β-estradiol mediated by A. niger RG13B1 involved hydroxylation, oxidation, methylation, acetylation, and dehydrogenation, especially infrequent lactylation, and the key degradation enzymes were found in the gene cluster of A. niger. In addition, we found that metabolite 12 interacted with amino acid residues Lys37, Gln39, Lys93, and Asn115 of NF-κB p65 to suppress expressions of inflammatory genes or proteins, exerting its anti-inflammatory effect. This study first illustrated the role of human gut microbe in 17β-estradiol degradation and provided new insights into its degradation mechanism by A. niger RG13B1.
环境激素因其对人类健康和生态安全的不利影响而引起了更多的关注。生物降解仍然是去除环境激素的有效策略,但人类肠道微生物在其降解中的作用仍有待阐明。在本工作中,我们旨在通过体外实验研究人类肠道微生物黑曲霉 RG13B1 对 17β-雌二醇(主要环境雌激素)的降解作用。其降解导致了十八种代谢产物的产生,这些代谢产物的特征是通过 H、C 和 2D NMR 以及 HRMS 谱确定的,包括九种新的(1-9)和九种已知的代谢产物(10-18)。基于它们的结构,黑曲霉 RG13B1 介导的 17β-雌二醇的降解途径涉及羟化、氧化、甲基化、乙酰化和脱氢作用,特别是罕见的乳酰化,关键的降解酶存在于黑曲霉的基因簇中。此外,我们发现代谢产物 12 与 NF-κB p65 的氨基酸残基 Lys37、Gln39、Lys93 和 Asn115 相互作用,抑制炎症基因或蛋白的表达,发挥其抗炎作用。本研究首次阐明了人类肠道微生物在 17β-雌二醇降解中的作用,并为黑曲霉 RG13B1 对其降解机制提供了新的见解。