Unusual Acyltransferase Negatively Regulates Nigericin Production via Malonylation of P450 NigD.
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| Format: | Artículo científico |
| Langue: | en |
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Journal of agricultural and food chemistry
2026
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| _version_ | 1868266056180563968 |
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| author | Yan, Yunchen Liu, Zengzhi Xing, Kaishuai Liu, Chunni Liu, Jing Deng, Zirong Yang, Xiaoyu Li, Hongcheng Xiao, Fei Li, Wenli |
| author_facet | Yan, Yunchen Liu, Zengzhi Xing, Kaishuai Liu, Chunni Liu, Jing Deng, Zirong Yang, Xiaoyu Li, Hongcheng Xiao, Fei Li, Wenli Yan, Yunchen Liu, Zengzhi Xing, Kaishuai Liu, Chunni Liu, Jing Deng, Zirong Yang, Xiaoyu Li, Hongcheng Xiao, Fei Li, Wenli |
| collection | PubMed - marine biology |
| contents | Unusual Acyltransferase Negatively Regulates Nigericin Production via Malonylation of P450 NigD. Yan, Yunchen Liu, Zengzhi Xing, Kaishuai Liu, Chunni Liu, Jing Deng, Zirong Yang, Xiaoyu Li, Hongcheng Xiao, Fei Li, Wenli Streptomyces Bacterial Proteins Cytochrome P-450 Enzyme System Nigericin Acyltransferases Malonates Gene Expression Regulation, Bacterial Secondary metabolism in is subjected to complex regulation. Compared to regulations on the transcriptional level, our knowledge of those on the post-translational level remains limited. Here, we identify a Gcn5-related -acetyltransferase, SyPmatA, in the marine-derived OUC6819, which negatively affects the production of nigericin, a polyether ionophore antibiotic with antifungal and antiparasitic activities. Inactivation of enhanced the nigericin yield by 5.2-fold. Using and assays, we demonstrate that SyPmatA specifically catalyzes malonylation of P450 NigD at K224, negatively modulating its function. Overexpression of (mimicking demalonylation) in the Δ mutant further increased nigericin production. Fermentation optimization and scale-up in a 5L-bioreactor using the engineered strain Δ/ achieved a final titer of 444.5 mg/L, representing a 61.9-fold improvement over the wild-type strain. Our findings reveal a novel lysine malonylation-mediated regulatory mechanism in nigericin biosynthesis and highlight the potential of targeting post-translational modification enzymes for metabolic engineering. |
| format | Artículo científico |
| id | pubmed_42033376 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of agricultural and food chemistry |
| record_format | pubmed |
| spellingShingle | Unusual Acyltransferase Negatively Regulates Nigericin Production via Malonylation of P450 NigD. Yan, Yunchen Liu, Zengzhi Xing, Kaishuai Liu, Chunni Liu, Jing Deng, Zirong Yang, Xiaoyu Li, Hongcheng Xiao, Fei Li, Wenli Streptomyces Bacterial Proteins Cytochrome P-450 Enzyme System Nigericin Acyltransferases Malonates Gene Expression Regulation, Bacterial Unusual Acyltransferase Negatively Regulates Nigericin Production via Malonylation of P450 NigD. Yan, Yunchen Liu, Zengzhi Xing, Kaishuai Liu, Chunni Liu, Jing Deng, Zirong Yang, Xiaoyu Li, Hongcheng Xiao, Fei Li, Wenli Streptomyces Bacterial Proteins Cytochrome P-450 Enzyme System Nigericin Acyltransferases Malonates Gene Expression Regulation, Bacterial Secondary metabolism in is subjected to complex regulation. Compared to regulations on the transcriptional level, our knowledge of those on the post-translational level remains limited. Here, we identify a Gcn5-related -acetyltransferase, SyPmatA, in the marine-derived OUC6819, which negatively affects the production of nigericin, a polyether ionophore antibiotic with antifungal and antiparasitic activities. Inactivation of enhanced the nigericin yield by 5.2-fold. Using and assays, we demonstrate that SyPmatA specifically catalyzes malonylation of P450 NigD at K224, negatively modulating its function. Overexpression of (mimicking demalonylation) in the Δ mutant further increased nigericin production. Fermentation optimization and scale-up in a 5L-bioreactor using the engineered strain Δ/ achieved a final titer of 444.5 mg/L, representing a 61.9-fold improvement over the wild-type strain. Our findings reveal a novel lysine malonylation-mediated regulatory mechanism in nigericin biosynthesis and highlight the potential of targeting post-translational modification enzymes for metabolic engineering. |
| title | Unusual Acyltransferase Negatively Regulates Nigericin Production via Malonylation of P450 NigD. |
| topic | Streptomyces Bacterial Proteins Cytochrome P-450 Enzyme System Nigericin Acyltransferases Malonates Gene Expression Regulation, Bacterial |
| url | https://pubmed.ncbi.nlm.nih.gov/42033376/ |