P450 Enzyme LyoI Performs Hydro-2,2'-Bifuran Oxidation in the Polyether Ionophore Lysocellin.

ABSTRACT: Polyether ionophores are potent antimicrobials, albeit also cytotoxic against mammalian cells. We have identified several polyether ionophores containing a common hydro-2,2'-bifuran-2-ol (hemiketal) moiety, which cannot be derived from the canonical biosynthetic steps observed for the compound class, suggesting an unusual oxidative transformation. To identify the responsible enzyme, we applied CRISPR-BEST to knock out genes in the lysocellin-producing strain S. longwoodensis. This allowed us to propose the first annotation of the lysocellin biosynthetic gene cluster and identify the responsible P450 enzyme, LyoI, through reconstitution of the function in vivo. LyoI knockout provided access to the non-oxidized precursor (pre-lysocellin) which allowed both in vitro validation of the unusual

SUBMITTER: Rasmussen MH 

PROVIDER: S-EPMC12535388 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature