Engineering <i>Yarrowia lipolytica</i> for high-level ergosterol production.

ABSTRACT: Ergosterol is the key precursor of steroid drug synthesis. In this experiment, we systematically modified the synthesis of ergosterol. Firstly, we identified key rate-limiting enzymes through systematic screening of the post-squalene pathway. Combinatorial overexpression of IDI1, tHMG1, ERG4, ERG5, ERG27, ERG1 and ERG11 achieved an ergosterol titer of 94.2 mg/L. Molecular dynamics guided mutagenesis of key substrate channel residues, particularly S372V Erg11, enhanced local flexibility and significantly increased ergosterol production. Introduction of the proton-donating mutations S372V-T305H-ERG11 established an artificial proton-dependent pathway, which, together with channel engineering, further increased the titer to 124 mg/L. Lip

SUBMITTER: Liu X 

PROVIDER: S-EPMC12855555 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature