Biosynthesis of lanosterol in Escherichia coli

Lipid composition represents a significant differentiator across the three domains (eukaryotes, bacteria, and archaea) of cellular life. Eukaryotes possess distinct lipids, such as sterols and sphingolipids, generally, these are not commonly found in typical bacteria and archaea. Sterols play a pivotal role in eukaryotic cellular functions, lanosterol, a key precursor for animal and fungal steroids, has well established functions in eukaryotes, while its potential functions in bacteria remain largely uninvestigated. In this study, we genetically engineered Escherichia coli (E. coli) to reconstruct the biosynthesis of lanosterol, and successfully developed a novel E. coli strain capable of synthesizing lanosterol, although its specific location, such as whether it is incorporated into the cell membrane, remains to be further determined. Comprehensive characterization of the observed phenotypic changes has unveiled that, despite an unaltered growth rate under normal condition, the engineered E. coli strain displayed notably enhanced tolerance to various stresses. Subsequent analysis has indicated that lanosterol plays a role in preserving membrane integrity, fluidity, hydrophobicity, and ATP production, mirroring the functions of sterols in eukaryotes. This study unveils the unexpected capacity of E. coli to synthesize sterols, not only underscores the importance of lanosterol as a precursor for essential cellular lipids but also offers fresh insights into the potential functions of sterols within bacterial systems.