Biosynthesis of tauro-ursodeoxycholic acid (TUDCA) in Saccharomyces cerevisiae

Tauroursodeoxycholic acid (TUDCA) is a microbial bile acid known for its diverse yet still largely unexplored biological activities. Traditionally used in Asian medicine, TUDCA and the taurine-free form, ursodeoxycholic acid (UDCA), share similar therapeutic properties. Recent studies suggest that TUDCA is a promising lead compound for developing neuroprotective agents to prevent neurodegenerative diseases such as Parkinson's disease and Huntington's disease. However, sustainable and ethical sources for large-scale TUDCA production remain unavailable. To address this, we are engineering a yeast-based microbial platform capable of producing TUDCA via fermentation. Here we report strains capable of converting the more widely available primary bile acid, chenodeoxycholic acid (CDCA) into TUDCA. This was achieved by introducing heterologous genes enabling taurine conjugation and taurine biosynthesis, providing a sustainable and scalable approach for TUDCA production.