ArticleMicrobial cell factories2024
Gene expression screening and cell factory engineering for enhancing echinocandin B production in Aspergillus nidulans NRRL8112.
Article in Microbial cell factories, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Identifying metabolic bottlenecks for micafungin precursor production via untargeted regulatory perturbation.Biotechnology for biofuels and bioproducts · 2026Article
- Regulation and induction of fungal secondary metabolites: a comprehensive review.Archives of microbiology · 2025Review
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9 authors.
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Abstract
backgroundEchinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin and its biosynthesis occurs via ani gene cluster in Aspergillus nidulans NRRL8112. Strain improvement for industrial ECB production has mainly relied on mutation breeding due to the lack of genetic tools.
resultsHere, a CRISPR-base-editing tool was developed in A. nidulans NRRL8112 for simultaneous inactivation of the nkuA gene and two marker genes, pryoA and riboB, which enabled efficient genetic manipulation. Then, in-vivo plasmid assembly was harnessed for ani gene expression screening, identifying the rate-limiting enzyme AniA and a pathway-specific transcription factor AniJ. Stepwise titer enhancement was achieved by overexpressing aniA and/or aniJ, and ECB production reached 1.5 g/L during 5-L fed-batch fermentation, an increase of ~ 30-fold compared with the parent strain.
conclusionThis study, for the first time, revealed the regulatory mechanism of ECB biosynthesis and harnessed genetic engineering for the development of an efficient ECB-producing strain.
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