# Microbial Synthesis and Biological Activity of 20β-Hydroxylated Progestins: Ovarian and Neural Action of 17α,20β,21α-Trihydroxy-4-Pregnen-3-One in Danio rerio

## TL;DR

Scientists used microbes to create a progestin compound that affects stress and anxiety in fish and activates hormone-related pathways in their brains and ovaries.

## Contribution

Discovery of a novel biologically active progestin and its microbial synthesis pathway with potential roles in teleost physiology.

## Key findings

- Streptomyces rochei efficiently biotransformed cortexolone into 20β-S with high yield.
- 20β-S modulates stress and anxiety behaviors in Danio rerio and activates Pgr-dependent transcription in brain and ovarian tissues.
- Microbial synthesis of 20-hydroxylated progestins can serve as bioregulators in teleosts.

## Abstract

In this study, the biocatalytic activity of four steroid-transforming strains isolated from the African frog Xenopus laevis and identified as Streptomyces rochei towards pregnane steroids has been investigated. All the isolated strains facilitated the reduction of the C20-carbonyl group and the structures of the metabolites were confirmed by mass spectrometric (MS) and 1H NMR spectroscopic analyses. Hydrocortisone and progesterone were poorly transformed by the streptomycete strains, whereas cortexolone (Reichstein’s substance S) was effectively biotransformed, yielding more than 90% of 17α,20β,21α-trihydroxy-4-pregnen-3-one (20β-S). Primarily, 20α-reduction was detected when the microbial isolates were incubated with 17α-hydroxyprogesterone with the yield of 17α,20α-dihydroxy-4-pregnen-3-one (17,20α-P) reaching 70%. The biological activity of 20β-S was evaluated in Danio rerio. The results demonstrated that 20β-S modulated stress- and anxiety-related behavioral responses and activated Pgr-dependent transcriptional pathways in the brain and ovarian tissues. These observations support the potential relevance of the synthesized progestin as a functional regulator in teleost physiology. The findings enhance our understanding of the biodiversity of steroid-transforming actinomycetes inhabiting amphibians and can be successfully employed for the effective microbiological synthesis of biologically active 20-hydroxylated progestins that serve as bioregulators in teleosts.