Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors
文献类型：期刊论文
| 作者 | Yu,Zhiyin; Huang,Jian-Ping; Yang,Jing ; Liu,Chongxi; Yan,Yijun; Wang,Li; Zhao,Junwei; Chen,Yin; Xiang,Wensheng; Huang,Sheng-Xiong
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| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2023 |
| 卷号 | 14期号:1页码:209 |
| 关键词 | HYPERTENSION PREDICTION FLAVIN MECHANISM PATHWAY OXIDASE COMPLEX DOMAIN SOIL |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-023-35829-1 |
| 英文摘要 | Angiotensin-converting enzyme inhibitors are widely used for treatment of hypertension and related diseases. Here, six karnamicins E-1-E-6 (1-6), which bear fully substituted hydroxypyridine and thiazole moieties are characterized from the rare actinobacterium Lechevalieria rhizosphaerae NEAU-A2. Through a combination of isotopic labeling, genome mining, and enzymatic characterization studies, the programmed assembly of the fully substituted hydroxypyridine moiety in karnamicin is proposed to be due to sequential operation of a hybrid polyketide synthase-nonribosomal peptide synthetase, two regioselective pyridine ring flavoprotein hydroxylases, and a methyltransferase. Based on AlphaFold protein structures predictions, molecular docking, and site-directed mutagenesis, we find that two pyridine hydroxylases deploy active site residues distinct from other flavoprotein monooxygenases to direct the chemo- and regioselective hydroxylation of the pyridine nucleus. Pleasingly, karnamicins show significant angiotensin-converting enzyme inhibitory activity with IC50 values ranging from 0.24 to 5.81 mu M, suggesting their potential use for the treatment of hypertension and related diseases. Treatment of hypertension entails use of angiotensin-converting enzyme inhibitors. Here, the authors show a series of karnamicins with significant inhibitory activity and identify two unusual flavoprotein hydroxylases involved in the assembly of the fully-substituted hydroxypyridine core of karnamicins. |
| 学科主题 | Science & Technology - Other Topics |
| WOS记录号 | WOS:000955813400006 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/74863]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Yu,Zhiyin,Huang,Jian-Ping,Yang,Jing,et al. Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors[J]. NATURE COMMUNICATIONS,2023,14(1):209. |
| APA | Yu,Zhiyin.,Huang,Jian-Ping.,Yang,Jing.,Liu,Chongxi.,Yan,Yijun.,...&Huang,Sheng-Xiong.(2023).Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors.NATURE COMMUNICATIONS,14(1),209. |
| MLA | Yu,Zhiyin,et al."Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors".NATURE COMMUNICATIONS 14.1(2023):209. |
入库方式： OAI收割
来源：昆明植物研究所
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