Degradation profile of environmental pollutant 17β-estradiol by human intestinal fungus Aspergillus niger RG13B1 and characterization of genes involved in its degradation

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 ¹H, ¹³C, 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.