Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin
Abstract Puerarin, daidzein C-glucoside, was known to be biotransformed to daidzein by human intestinal bacteria, which is eventually converted to (S)-equol. The metabolic pathway of puerarin to daidzein by DgpABC of Dorea sp. PUE strain was reported as puerarin (1) → 3’’-oxo-puerarin (2) → daidzein...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-43379-1 |
| _version_ | 1797559997833412608 |
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| author | Jongkeun Choi Yongho Kim Bekir Engin Eser Jaehong Han |
| author_facet | Jongkeun Choi Yongho Kim Bekir Engin Eser Jaehong Han |
| author_sort | Jongkeun Choi |
| collection | DOAJ |
| description | Abstract Puerarin, daidzein C-glucoside, was known to be biotransformed to daidzein by human intestinal bacteria, which is eventually converted to (S)-equol. The metabolic pathway of puerarin to daidzein by DgpABC of Dorea sp. PUE strain was reported as puerarin (1) → 3’’-oxo-puerarin (2) → daidzein (3) + hexose enediolone (C). The second reaction is the cleavage of the glycosidic C–C bond, supposedly through the quinoid intermediate (4). In this work, the glycosidic C–C bond cleavage reaction of 3’’-oxo-puerarin (2) was theoretically studied by means of DFT calculation to elucidate chemical reaction mechanism, along with biochemical energetics of puerarin metabolism. It was found that bioenergetics of puerarin metabolism is slightly endergonic by 4.99 kcal/mol, mainly due to the reaction step of hexose enediolone (C) to 3’’-oxo-glucose (A). The result implied that there could be additional biochemical reactions for the metabolism of hexose enediolone (C) to overcome the thermodynamic energy barrier of 4.59 kcal/mol. The computational study focused on the C–C bond cleavage of 3’’-oxo-puerarin (2) found that formation of the quinoid intermediate (4) was not accessible thermodynamically, rather the reaction was initiated by the deprotonation of 2’’C–H proton of 3’’-oxo-puerarin (2). The 2’’C-dehydro-3’’-oxo-puerarin (2a2C) anionic species produced hexose enediolone (C) and 8-dehydro-daidzein anion (3a8), and the latter quickly converted to daidzein through the daidzein anion (3a7). Our study also explains why the reverse reaction of C-glycoside formation from daidzein (3) and hexose enediolone (C) is not feasible. |
| first_indexed | 2024-03-10T17:53:14Z |
| format | Article |
| id | doaj.art-c42a09f697564ecd899d86e19f51f180 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:53:14Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c42a09f697564ecd899d86e19f51f1802023-11-20T09:17:12ZengNature PortfolioScientific Reports2045-23222023-09-0113111010.1038/s41598-023-43379-1Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarinJongkeun Choi0Yongho Kim1Bekir Engin Eser2Jaehong Han3Department of Chemical Engineering, Chungwoon UniversityDepartment of Applied Chemistry, Institute of Applied Sciences, Kyung Hee UniversityDepartment of Biological and Chemical Engineering, Aarhus UniversityMetalloenzyme Research Group, Department of Plant Science and Technology, Chung-Ang UniversityAbstract Puerarin, daidzein C-glucoside, was known to be biotransformed to daidzein by human intestinal bacteria, which is eventually converted to (S)-equol. The metabolic pathway of puerarin to daidzein by DgpABC of Dorea sp. PUE strain was reported as puerarin (1) → 3’’-oxo-puerarin (2) → daidzein (3) + hexose enediolone (C). The second reaction is the cleavage of the glycosidic C–C bond, supposedly through the quinoid intermediate (4). In this work, the glycosidic C–C bond cleavage reaction of 3’’-oxo-puerarin (2) was theoretically studied by means of DFT calculation to elucidate chemical reaction mechanism, along with biochemical energetics of puerarin metabolism. It was found that bioenergetics of puerarin metabolism is slightly endergonic by 4.99 kcal/mol, mainly due to the reaction step of hexose enediolone (C) to 3’’-oxo-glucose (A). The result implied that there could be additional biochemical reactions for the metabolism of hexose enediolone (C) to overcome the thermodynamic energy barrier of 4.59 kcal/mol. The computational study focused on the C–C bond cleavage of 3’’-oxo-puerarin (2) found that formation of the quinoid intermediate (4) was not accessible thermodynamically, rather the reaction was initiated by the deprotonation of 2’’C–H proton of 3’’-oxo-puerarin (2). The 2’’C-dehydro-3’’-oxo-puerarin (2a2C) anionic species produced hexose enediolone (C) and 8-dehydro-daidzein anion (3a8), and the latter quickly converted to daidzein through the daidzein anion (3a7). Our study also explains why the reverse reaction of C-glycoside formation from daidzein (3) and hexose enediolone (C) is not feasible.https://doi.org/10.1038/s41598-023-43379-1 |
| spellingShingle | Jongkeun Choi Yongho Kim Bekir Engin Eser Jaehong Han Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin Scientific Reports |
| title | Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin |
| title_full | Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin |
| title_fullStr | Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin |
| title_full_unstemmed | Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin |
| title_short | Theoretical study on the glycosidic C–C bond cleavage of 3’’-oxo-puerarin |
| title_sort | theoretical study on the glycosidic c c bond cleavage of 3 oxo puerarin |
| url | https://doi.org/10.1038/s41598-023-43379-1 |
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