Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines
Abstract Tetrahydroisoquinoline alkaloids (THIQAs) are ubiquitous compounds with important pharmaceutical and biological activity. Their key N-heterocyclic structural motifs are synthesised via Pictet–Spengler (P–S) reaction by norcoclaurine synthases (NCS) in plants. The synthesis of 1-aryl-tetrahy...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-03-01
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| Series: | Bioresources and Bioprocessing |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40643-023-00637-4 |
| _version_ | 1797865679529967616 |
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| author | Man Zhang Zheng-Yu Huang Ying Su Fei-Fei Chen Qi Chen Jian-He Xu Gao-Wei Zheng |
| author_facet | Man Zhang Zheng-Yu Huang Ying Su Fei-Fei Chen Qi Chen Jian-He Xu Gao-Wei Zheng |
| author_sort | Man Zhang |
| collection | DOAJ |
| description | Abstract Tetrahydroisoquinoline alkaloids (THIQAs) are ubiquitous compounds with important pharmaceutical and biological activity. Their key N-heterocyclic structural motifs are synthesised via Pictet–Spengler (P–S) reaction by norcoclaurine synthases (NCS) in plants. The synthesis of 1-aryl-tetrahydroisoquinoline alkaloids has attracted increasing attention due to their antitumor and antivirus activities. Herein, the L68T/M97V mutant of NCS from Thalictrum flavum with improved activity was developed by semi-rational design. This mutant not only showed higher catalytic performance (> 96% conversion) toward benzaldehyde and dopamine over the wild-type enzyme, but also catalysed the P–S reaction of the bulky substrate 4-biphenylaldehyde and dopamine with high conversion (> 99%) for the effective synthesis of 1-aryl-THIQA. In terms of stereoselectivity, all products synthesised by the L68T/M97V mutant showed high optical purity (92–99% enantiomeric excess). Graphical Abstract |
| first_indexed | 2024-04-09T23:13:10Z |
| format | Article |
| id | doaj.art-7fbf4f69b2d14c418c6028ca9744eb1b |
| institution | Directory Open Access Journal |
| issn | 2197-4365 |
| language | English |
| last_indexed | 2024-04-09T23:13:10Z |
| publishDate | 2023-03-01 |
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| series | Bioresources and Bioprocessing |
| spelling | doaj.art-7fbf4f69b2d14c418c6028ca9744eb1b2023-03-22T10:17:49ZengSpringerOpenBioresources and Bioprocessing2197-43652023-03-0110111010.1186/s40643-023-00637-4Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolinesMan Zhang0Zheng-Yu Huang1Ying Su2Fei-Fei Chen3Qi Chen4Jian-He Xu5Gao-Wei Zheng6State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, College of Biotechnology, East China University of Science and TechnologyAbstract Tetrahydroisoquinoline alkaloids (THIQAs) are ubiquitous compounds with important pharmaceutical and biological activity. Their key N-heterocyclic structural motifs are synthesised via Pictet–Spengler (P–S) reaction by norcoclaurine synthases (NCS) in plants. The synthesis of 1-aryl-tetrahydroisoquinoline alkaloids has attracted increasing attention due to their antitumor and antivirus activities. Herein, the L68T/M97V mutant of NCS from Thalictrum flavum with improved activity was developed by semi-rational design. This mutant not only showed higher catalytic performance (> 96% conversion) toward benzaldehyde and dopamine over the wild-type enzyme, but also catalysed the P–S reaction of the bulky substrate 4-biphenylaldehyde and dopamine with high conversion (> 99%) for the effective synthesis of 1-aryl-THIQA. In terms of stereoselectivity, all products synthesised by the L68T/M97V mutant showed high optical purity (92–99% enantiomeric excess). Graphical Abstracthttps://doi.org/10.1186/s40643-023-00637-4BiocatalysisNorcoclaurine synthaseProtein engineeringPictet–Spengler reactionTetrahydroisoquinoline alkaloids |
| spellingShingle | Man Zhang Zheng-Yu Huang Ying Su Fei-Fei Chen Qi Chen Jian-He Xu Gao-Wei Zheng Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines Bioresources and Bioprocessing Biocatalysis Norcoclaurine synthase Protein engineering Pictet–Spengler reaction Tetrahydroisoquinoline alkaloids |
| title | Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines |
| title_full | Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines |
| title_fullStr | Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines |
| title_full_unstemmed | Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines |
| title_short | Engineering a norcoclaurine synthase for one-step synthesis of (S)-1-aryl-tetrahydroisoquinolines |
| title_sort | engineering a norcoclaurine synthase for one step synthesis of s 1 aryl tetrahydroisoquinolines |
| topic | Biocatalysis Norcoclaurine synthase Protein engineering Pictet–Spengler reaction Tetrahydroisoquinoline alkaloids |
| url | https://doi.org/10.1186/s40643-023-00637-4 |
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