Gut Bacteria Encode Reductases that Biotransform Steroid Hormones.

ABSTRACT: The metabolism of steroids by the gut microbiome affects hormone homeostasis, impacting host development, mental health, and reproductive functions. In this study, we identify the Δ⁴-3-ketosteroid 5β-reductase, 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase, and Δ⁶-3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, We show that 5β-reductase and Δ⁶-3-ketosteroid reductase have evolved to specialize in converting diverse 3-keto steroid hormones into their 5β- and Δ⁶-reduced derivatives. We also find that the novel 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase is fused with 5β-reductase in multiple species, streamlining the multi-step conversion of

SUBMITTER: Arp G 

PROVIDER: S-EPMC11722256 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature