Side-Chain Macrocyclization in Ahp-Bicyclodepsipeptides Biosynthesis Involves Cytochrome P450-Catalyzed Sequential Aromatic Hydroxylation and C―N Coupling
文献类型：期刊论文
| 作者 | Dong, Qiang1; Zhang, Niandi2; Chen, Xiaorong1; Xuan, Jiayi3,5; Huang, Tai3; Niu, Bo1; Xu, Zhefei1; Hu, Qingsong1; Chen, Jiayi4,6; Zhang, Zhuan2 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2025-10-18 |
| 页码 | 7 |
| 关键词 | Biosynthesis C & horbar Genome mining Nonribosomal peptides Side-chain macrocyclization N coupling |
| DOI | 10.1002/anie.202513520 |
| 英文摘要 | We report the biosynthesis of FR901277 (1) and delmomycin A2 (2), two 3-amino-6-hydroxypiperidone (Ahp)-containing bicyclodepsipeptides featuring an N-C bridge linking the citrulline and tyrosine residues. This intriguing side-chain macrocyclization is catalyzed by Dlm16, a cytochrome P450 monooxygenase (CYP450), through a sequential process initiated by ortho-hydroxylation of the tyrosine ring, followed by intramolecular C & horbar;N coupling between the resulting catechol moiety and the terminal NH2 of the ureido group. Structure-function analyses and site-directed mutagenesis confirmed the catalytic importance of identified key residues, enabling the proposal of plausible macrocyclization mechanisms. Functional characterization of eight additional Dlm16 homologs further revealed a CYP450 subfamily capable of catalyzing C & horbar;N bond formation, underscoring the prevalence of this unusual macrocyclization in cyclodepsipeptide biosynthesis. Our work highlights nature's strategies for macrocycle construction and provides another example of CYP450-catalyzed C & horbar;N coupling via direct C & horbar;H functionalization. |
| WOS关键词 | HUMAN-LEUKOCYTE ELASTASE ; INHIBITOR ; FR901277 ; VANCOMYCIN ; PROTEIN ; PEPTIDE ; PATHWAY |
| 资助项目 | CAMS Innovation fund for Medical Sciences |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001595818200001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/320650]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Zhang, Zhuan; Meng, Song |
| 作者单位 | 1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China 2.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, NHC Key Lab Biotechnol Microbial Drugs, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China 3.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Res Ctr, Shanghai 201203, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Qiang,Zhang, Niandi,Chen, Xiaorong,et al. Side-Chain Macrocyclization in Ahp-Bicyclodepsipeptides Biosynthesis Involves Cytochrome P450-Catalyzed Sequential Aromatic Hydroxylation and C―N Coupling[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2025:7. |
| APA | Dong, Qiang.,Zhang, Niandi.,Chen, Xiaorong.,Xuan, Jiayi.,Huang, Tai.,...&Meng, Song.(2025).Side-Chain Macrocyclization in Ahp-Bicyclodepsipeptides Biosynthesis Involves Cytochrome P450-Catalyzed Sequential Aromatic Hydroxylation and C―N Coupling.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,7. |
| MLA | Dong, Qiang,et al."Side-Chain Macrocyclization in Ahp-Bicyclodepsipeptides Biosynthesis Involves Cytochrome P450-Catalyzed Sequential Aromatic Hydroxylation and C―N Coupling".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2025):7. |
入库方式： OAI收割
来源：上海药物研究所
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