Jie Chen, Fuquan Yao, Yiping Jiang, Xiangquan Qin, Mo Xian, Yingang Feng, Zhiqi Cong
{"title":"Diverse N-Oxidation of Primary Aromatic Amines Controlled by Engineered P450 Peroxizyme Variants Facilitated by Dual-Functional Small Molecule.","authors":"Jie Chen, Fuquan Yao, Yiping Jiang, Xiangquan Qin, Mo Xian, Yingang Feng, Zhiqi Cong","doi":"10.1002/advs.202412100","DOIUrl":null,"url":null,"abstract":"<p><p>Amine oxidation is an important organic reaction for the production of high-value N-containing compounds. However, it is still challenging to control the reactivity of active N-centered radicals to selectively access N-oxidation products. Herein, this study reports the engineering of cytochrome P450BM3 into multifunctional N-oxidizing enzymes with the assistance of dual-functional small molecules (DFSM) to selectively produce N-oxygenation (i.e., p-nitrosobenzene, p-nitrobenzene, and azoxybenzene) and one-electron oxidation products (i.e., oligomeric quinones and azobenzene) from aromatic amines. The best mutant, F87A/T268V/V78T/A82T, exclusively gives p-nitrosobenzene (up to 98% selectivity), whereas the selectivity for p-nitrobenzene is >99% using the mutant F87A/T268V/A82T/I263L. Crystal structure analysis reveals that key mutations and DFSM exert synergistic effects on catalytic promiscuity by controlling the substrate orientation in active center. This study highlights the potential of DFSM-facilitated P450 peroxygenase and peroxidase for the synthesis of N-containing compounds via the controllable oxidation of aromatic amines, substantially expanding the chemical space of P450 enzymes.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2412100"},"PeriodicalIF":14.3000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202412100","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Amine oxidation is an important organic reaction for the production of high-value N-containing compounds. However, it is still challenging to control the reactivity of active N-centered radicals to selectively access N-oxidation products. Herein, this study reports the engineering of cytochrome P450BM3 into multifunctional N-oxidizing enzymes with the assistance of dual-functional small molecules (DFSM) to selectively produce N-oxygenation (i.e., p-nitrosobenzene, p-nitrobenzene, and azoxybenzene) and one-electron oxidation products (i.e., oligomeric quinones and azobenzene) from aromatic amines. The best mutant, F87A/T268V/V78T/A82T, exclusively gives p-nitrosobenzene (up to 98% selectivity), whereas the selectivity for p-nitrobenzene is >99% using the mutant F87A/T268V/A82T/I263L. Crystal structure analysis reveals that key mutations and DFSM exert synergistic effects on catalytic promiscuity by controlling the substrate orientation in active center. This study highlights the potential of DFSM-facilitated P450 peroxygenase and peroxidase for the synthesis of N-containing compounds via the controllable oxidation of aromatic amines, substantially expanding the chemical space of P450 enzymes.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.