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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Microbial cell factories
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41233853/ |
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Table of Contents:
- Multi-layered engineering of Aspergillus terreus enhances biosynthesis of the plant-derived fungicide physcion. Ren, Zilin Xue, Yingying Xu, Ning Feng, Dandan Geng, Ce Wu, Yongsong Liu, Dan Zhao, Linshui Zhang, Xiaoxi Ma, Honglei Huang, Xuenian Qi, Feifei Lu, Xuefeng Aspergillus Emodin Fungicides, Industrial Cytochrome P-450 Enzyme System Metabolic Engineering Fungal Proteins Anthraquinones Emodin and its derivatives are important bioactive anthraquinones from rhubarb, with diverse pharmacological activities. Physcion, an O-methylated derivative of emodin, is a promising plant-derived fungicide and pharmaceutical lead. However, plant extraction yields are low and land-intensive, while microbial production is hampered by inefficient conversion and byproduct accumulation. Here, we identify a cytochrome P450 enzyme (CYP-H6231) that, with its dedicated redox partner cytochrome P450 reductase (CPR-H10273), converts emodin to ω-hydroxyemodin in Aspergillus terreus. Deletion of CYP-H6231 increased physcion titer by 1.8-fold and significantly improved product purity. Further engineering, via 3-O-methyltransferase overexpression, SAM pathway enhancement, and enzyme fusion, yielded only modest improvement (up to 37%), likely due to compromised strain robustness from the loss of CYP-H6231 mediated detoxification. Structural modeling and mutagenesis of CYP-H6231 revealed key residues for substrate recognition and catalysis. This study reveals a detoxification bottleneck in anthraquinone biosynthesis and establishes two improved A. terreus platforms for scalable production of physcion and emodin, respectively, highlighting trade-offs between pathway efficiency and cellular fitness.