Abstract B034: Characterization of a dual steroid 3β-,17β-oxidoreductase in the gut bacterium Eggerthella lenta

Abstract

Abstract As of 2023 there are over 200,000 new cases and over 30,000 deaths caused by prostate cancer with African-American (AA) men having a higher incidence then other ethnicities according to the American Cancer Society. Although numerous therapeutic methods are used to treat prostate cancer such as hormone therapy, radiation therapy, chemotherapy, and chemical castration, prostate cancer often becomes metastatic resulting in death with the five year survival rate for AA men presenting with castration resistant prostate cancer (CRPC) being ~ 32%. Androgen production is known to be the main driver of CRPC progression. Researchers are baffled as to why this progression is taking place after patients have received a combination of these therapeutic methods to stop androgen production and metabolism. Eggerthella lenta has a long history as an important bile acid and steroid metabolizing gut microbial species. We and others have previously published on the extensive oxidation and epimerization of bile acid hydoxyl groups. Previous work demonstrated that E. lenta may be involved in the conversion of 17-keto steroids to testosterone. By cloning, expressing, and purifying genes predicted to encode pyridine nucleotide-dependent oxidoreductases from E. lenta DSM 2243, we identified a recombinant enzyme with dual 3beta, 17beta-hydroxysteroid dehydrogenase activity. We performed kinetic analysis on both 5alpha-reduced bile acids ("allo"-bile acids) and 5alpha-reduced steroids. There is a paucity of work at present on gut bacteria that metabolize the 17beta-hydroxy group on steroids, so this observation demonstrates that a unique enzyme in the gut microbiome can alter host steroids. These findings are consistent with the possibility that gut or urinary tract bacteria may contribute to CRPC. Citation Format: Briawna J. Binion, Rex Gaskins, Jason Ridlon. Characterization of a dual steroid 3β-,17β-oxidoreductase in the gut bacterium Eggerthella lenta [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B034.