Characterization of an NADPH-dependent 17β-hydroxysteroid dehydrogenase from a urinary tract bacterial isolate.

Androgens are a class of steroid hormones that play essential roles in somatic development, reproductive physiology, and anabolic processes in both males and females. Beyond their physiological importance, androgens are implicated in the pathogenesis of several diseases and contribute to the progression of hormone-sensitive malignancies such as prostate, breast, lung, and ovarian cancers. The metabolic conversion of androgens is primarily catalyzed by two major enzyme classes: cytochrome P450 monooxygenases and NAD(P)H-dependent hydroxysteroid dehydrogenases (HSDHs). While endogenous androgen biosynthesis occurs predominantly in the testes, ovaries, adrenal glands, and placenta, emerging evidence suggests that host-associated microbial communities, including those residing in the urinary tract, may also contribute to local androgen metabolism. In our previous work, we identified the desG gene from the urinary tract isolate Propionimicrobium lymphophilum strain API-1, which encodes a novel NADPH-dependent 17β-HSDH. This enzyme catalyzes the bidirectional conversion between androstenedione (AD) and testosterone (T), suggesting a microbial route for androgen production within the urinary tract. In the present study, we expand on these findings by conducting detailed kinetic and substrate-specificity analyses of this enzyme, alongside bioconversion assays using a broad panel of steroid substrates. These results shed light on the steroid-transforming potential of urinary bacteria.

IMPORTANCE

This work represents an important advance in the understanding of androgen metabolism by urinary tract bacteria through the characterization of an NADPH-dependent 17β-HSDH encoded by the desG gene. By elucidating kinetic properties, substrate specificity, and bioconversion capabilities of recombinant DesG, this research provides valuable insights into steroid hormone regulation.