Generation of Novel Natural Products by Disrupting Azaphilone Synthesis in E23Y-1A.
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| Natura: | Artículo científico |
| Lingua: | en |
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Marine drugs
2026
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| _version_ | 1868266069634842626 |
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| author | Chang, Wenjun Yang, Yanhua Duan, Ruijun Qin, Heye Chen, Shiwen Zeng, Yanbo |
| author_facet | Chang, Wenjun Yang, Yanhua Duan, Ruijun Qin, Heye Chen, Shiwen Zeng, Yanbo Chang, Wenjun Yang, Yanhua Duan, Ruijun Qin, Heye Chen, Shiwen Zeng, Yanbo |
| collection | PubMed - marine biology |
| contents | Generation of Novel Natural Products by Disrupting Azaphilone Synthesis in E23Y-1A. Chang, Wenjun Yang, Yanhua Duan, Ruijun Qin, Heye Chen, Shiwen Zeng, Yanbo Biological Products Humans Pigments, Biological Benzopyrans Penicillium Cell Line, Tumor Antineoplastic Agents Multigene Family Marine-derived filamentous fungi are a rich source of structurally diverse and biologically active natural products. However, many biosynthetic gene clusters (BGCs) in fungi remain silent under standard conditions. In this study, we employed a metabolic shunting strategy to disrupt azaphilone biosynthesis in the marine-derived fungus E23Y-1A by deleting the pathway-specific regulator gene . HPLC analysis revealed the emergence of new metabolite peaks in the mutant strain Δ667 compared to the wild type. Subsequent purification yielded seven compounds: the mutant produced two novel meroterpenoids sclerotilins A and B ( and ) along with the known steroids ergosta-5,7,22-trien-3-ol () and cerevisterol (), while the wild type yielded the known steroid (22)-5α,8α-epidioxyergosta-6,22-dien-3-ol () and two azaphilones geumsanol G () and 5-chloro-3-[(1,3,4,5)-3,4-dihydroxy-3,5-dimethyl-1-hepten-1-yl]-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-(7,8,8a)-6-2-benzopyran-6-one (). Bioactivity assays showed that compound exhibited moderate antimicrobial activity against , and compound displayed moderate cytotoxicity against five human cancer cell lines. These results demonstrate that is essential for azaphilone biosynthesis and that its disruption leads to the production of structurally distinct natural products, highlighting the potential of pathway engineering to redirect fungal metabolism to yield novel natural products. |
| format | Artículo científico |
| id | pubmed_41892954 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Marine drugs |
| record_format | pubmed |
| spellingShingle | Generation of Novel Natural Products by Disrupting Azaphilone Synthesis in E23Y-1A. Chang, Wenjun Yang, Yanhua Duan, Ruijun Qin, Heye Chen, Shiwen Zeng, Yanbo Biological Products Humans Pigments, Biological Benzopyrans Penicillium Cell Line, Tumor Antineoplastic Agents Multigene Family Generation of Novel Natural Products by Disrupting Azaphilone Synthesis in E23Y-1A. Chang, Wenjun Yang, Yanhua Duan, Ruijun Qin, Heye Chen, Shiwen Zeng, Yanbo Biological Products Humans Pigments, Biological Benzopyrans Penicillium Cell Line, Tumor Antineoplastic Agents Multigene Family Marine-derived filamentous fungi are a rich source of structurally diverse and biologically active natural products. However, many biosynthetic gene clusters (BGCs) in fungi remain silent under standard conditions. In this study, we employed a metabolic shunting strategy to disrupt azaphilone biosynthesis in the marine-derived fungus E23Y-1A by deleting the pathway-specific regulator gene . HPLC analysis revealed the emergence of new metabolite peaks in the mutant strain Δ667 compared to the wild type. Subsequent purification yielded seven compounds: the mutant produced two novel meroterpenoids sclerotilins A and B ( and ) along with the known steroids ergosta-5,7,22-trien-3-ol () and cerevisterol (), while the wild type yielded the known steroid (22)-5α,8α-epidioxyergosta-6,22-dien-3-ol () and two azaphilones geumsanol G () and 5-chloro-3-[(1,3,4,5)-3,4-dihydroxy-3,5-dimethyl-1-hepten-1-yl]-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-(7,8,8a)-6-2-benzopyran-6-one (). Bioactivity assays showed that compound exhibited moderate antimicrobial activity against , and compound displayed moderate cytotoxicity against five human cancer cell lines. These results demonstrate that is essential for azaphilone biosynthesis and that its disruption leads to the production of structurally distinct natural products, highlighting the potential of pathway engineering to redirect fungal metabolism to yield novel natural products. |
| title | Generation of Novel Natural Products by Disrupting Azaphilone Synthesis in E23Y-1A. |
| topic | Biological Products Humans Pigments, Biological Benzopyrans Penicillium Cell Line, Tumor Antineoplastic Agents Multigene Family |
| url | https://pubmed.ncbi.nlm.nih.gov/41892954/ |