Metabolic engineering of Glarea lozoyensis for high-level production of pneumocandin B₀.

ABSTRACT: Pneumocandin B₀ (PB₀) is a lipohexapeptide synthesized by Glarea lozoyensis and serves as the precursor for the widely used antifungal drug caspofungin acetate (Cancidas®). However, the low titer of PB₀ results in fermentation and purification costs during caspofungin production, limiting its widespread clinical application. Here, we engineered an efficient PB₀-producing strain of G. lozoyensis by systems metabolic engineering strategies, including multi-omics analysis and multilevel metabolic engineering. We overexpressed four rate-limiting enzymes: thioesterase GLHYD, two cytochrome P450s GLP450s, and chorismate synthase GLCS; knocked out two competing pathways responsible for producing 6-methylsalicylic acid and pyranidine E; and

SUBMITTER: Zhang X 

PROVIDER: S-EPMC11742615 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature