Tetrahymena thermophila: a unique model for understanding sterol metabolism and its potential applications in drug discovery

A. D. NUSBLAT

Conferencia; Ciliate Molecular Biology conference; 2024

The single-celled Tetrahymena thermophila uniquely modifies dietary sterols, includingdesaturations and a de-ethylation. This, along with its lack of canonical C22 steroldesaturases, makes it ideal for studying unconventional sterol metabolism.Transcriptome analysis revealed novel C22 sterol desaturases belonging to a distinct enzymefamily. Cholesterol feeding suppressed genes for its own synthesis, favoring an alternativepathway. Additionally, potential transporters and signaling genes were identified.Functional studies confirmed two C22 sterol desaturases, representing a new enzyme typewithin the fatty acid hydroxylase/desaturase superfamily, likely arising from gene duplication.This highlights the existence of non-homologous enzymes with similar functions and the powerof T. thermophila in understanding enzyme evolution.Furthermore, Tetrahymena C7 sterol desaturase, absent in mammals but crucial for someparasites, presents a potential drug target. Characterization of C7SD and development ofinhibitors could lead to novel antiparasitic and insecticidal drugs.