Metabolic engineering of Glarea lozoyensis for high-level production of pneumocandin B0
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 widesp...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-06-01
|
| Series: | Synthetic and Systems Biotechnology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X24001601 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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 overexpressed the global transcriptional activator GLHYP. As a result, the PB0 titer increased by 108.7 % to 2.63 g/L at the shake-flask level through combinatorial strategies. Our study provides valuable insights into achieving high-level production of PB0 and offers general guidance for developing efficient fungal cell factories to produce polyketide synthase-non-ribosomal peptide synthetase hybrid metabolites. |
|---|---|
| ISSN: | 2405-805X |