Understand the Specific Regio- and Enantioselectivity of Fluostatin Conjugation in the Post-Biosynthesis
文献类型：期刊论文
| 作者 | Wang, Yuanqi; Zhang, Changsheng3; Zhao, Yi-Lei; Zhao, Rosalinda; Houk, Kendall N. |
| 刊名 | BIOMOLECULES
 |
| 出版日期 | 2020 |
| 卷号 | 10期号:6页码:815 |
| 关键词 | fluostatin conjugation regioselectivity stereoselectivity pi-pi stacking interaction |
| DOI | 10.3390/biom10060815 |
| 英文摘要 | Fluostatins, benzofluorene-containing aromatic polyketides in the atypical angucycline family, conjugate into dimeric and even trimeric compounds in the post-biosynthesis. The formation of the C-C bond involves a non-enzymatic stereospecific coupling reaction. In this work, the unusual regio- and enantioselectivities were rationalized by density functional theory calculations with the M06-2X (SMD, water)/6-311 + G(d,p)//6-31G(d) method. These DFT calculations reproduce the lowest energy C1-(R)-C10'-(S) coupling pathway observed in a nonenzymatic reaction. Bonding of the reactive carbon atoms (C1 and C10') of the two reactant molecules maximizes the HOMO-LUMO interactions and Fukui function involving the highest occupied molecular orbital (HOMO) of nucleophilep-QMand lowest unoccupied molecular orbital (LUMO) of electrophileFST(2)(-)anion. In particular, the significant pi-pi stacking interactions of the low-energy pre-reaction state are retained in the lowest energy pathway for C-C coupling. The distortion/interaction-activation strain analysis indicates that the transition state (TScp-I) of the lowest energy pathway involves the highest stabilizing interactions and small distortion among all possible C-C coupling reactions. One of the two chiral centers generated in this step is lost upon aromatization of the phenol ring in the final difluostatin products. Thus, the pi-pi stacking interactions between the fluostatin 6-5-6 aromatic ring system play a critical role in the stereoselectivity of the nonenzymatic fluostatin conjugation. |
| 资助机构 | National Key R&D Program of China [2018YFA0901200]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31970041, 31770070, 31820103003]; SJTU JiRLMDS Joint Research Fund [MDS-JF-2019A01] ; National Key R&D Program of China [2018YFA0901200]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31970041, 31770070, 31820103003]; SJTU JiRLMDS Joint Research Fund [MDS-JF-2019A01] |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/18406]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 作者单位 | 1.Zhao, Yi-Lei; Zhao, Rosalinda; Houk, Kendall N.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA 2.Chinese Acad Sci, RNAM Ctr Marine Microbiol, Key Lab Trop Marine Bioresource & Ecol, South China Sea Inst Oceanol,Guangdong Key Lab Ma, 164 West Xingang Rd, Guangzhou 510301, Peoples R China 3.Shanghai Jiao Tong Univ, Joint Int Res Lab Metab & Dev Sci, State Key Lab Microbial Metab, Sch Life Sci & Biotechnol, 800 Dongchuan Rd, Shanghai 200240, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yuanqi,Zhang, Changsheng,Zhao, Yi-Lei,et al. Understand the Specific Regio- and Enantioselectivity of Fluostatin Conjugation in the Post-Biosynthesis[J]. BIOMOLECULES,2020,10(6):815. |
| APA | Wang, Yuanqi,Zhang, Changsheng,Zhao, Yi-Lei,Zhao, Rosalinda,&Houk, Kendall N..(2020).Understand the Specific Regio- and Enantioselectivity of Fluostatin Conjugation in the Post-Biosynthesis.BIOMOLECULES,10(6),815. |
| MLA | Wang, Yuanqi,et al."Understand the Specific Regio- and Enantioselectivity of Fluostatin Conjugation in the Post-Biosynthesis".BIOMOLECULES 10.6(2020):815. |
入库方式： OAI收割
来源：南海海洋研究所
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