Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket
Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthase...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-06-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X24000413 |
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| author | Xinye Wang Yiyi Huang Weiyan Zhang Kangjie Lv Xiaoying Li Zhixin Wang Li Zhang Tom Hsiang Lixin Zhang Liming Ouyang Xueting Liu |
| author_facet | Xinye Wang Yiyi Huang Weiyan Zhang Kangjie Lv Xiaoying Li Zhixin Wang Li Zhang Tom Hsiang Lixin Zhang Liming Ouyang Xueting Liu |
| author_sort | Xinye Wang |
| collection | DOAJ |
| description | Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space. In this study, we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase (FoFS) by a single mutation at L89, leading to the production of three new sesterterpenes. Further computational analysis revealed that the reconstitution of the hydrogen-bond (H-bond) network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket. Thus, the dynamic orientation of W69 alters the carbocation transport, leading to the production of diverse ring system skeletons. These findings enhance our knowledge on understanding the molecular mechanisms, which could be applied on protein engineering terpene synthases on regulating the terpene skeletons. |
| first_indexed | 2024-04-24T20:04:53Z |
| format | Article |
| id | doaj.art-bcda50246e9843269eb1c0ddeb3d3eda |
| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T20:04:53Z |
| publishDate | 2024-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-bcda50246e9843269eb1c0ddeb3d3eda2024-03-24T06:59:28ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2024-06-0192380387Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocketXinye Wang0Yiyi Huang1Weiyan Zhang2Kangjie Lv3Xiaoying Li4Zhixin Wang5Li Zhang6Tom Hsiang7Lixin Zhang8Liming Ouyang9Xueting Liu10State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaDepartment of Chemistry, Boston University, Boston, MA, USASchool of Environmental Sciences, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, CanadaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Corresponding author.State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Corresponding author.Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space. In this study, we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase (FoFS) by a single mutation at L89, leading to the production of three new sesterterpenes. Further computational analysis revealed that the reconstitution of the hydrogen-bond (H-bond) network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket. Thus, the dynamic orientation of W69 alters the carbocation transport, leading to the production of diverse ring system skeletons. These findings enhance our knowledge on understanding the molecular mechanisms, which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.http://www.sciencedirect.com/science/article/pii/S2405805X24000413Bifunctional terpene synthaseSesterterpeneCarbocation transportationDensity functional theory calculationsMolecular dynamics simulations |
| spellingShingle | Xinye Wang Yiyi Huang Weiyan Zhang Kangjie Lv Xiaoying Li Zhixin Wang Li Zhang Tom Hsiang Lixin Zhang Liming Ouyang Xueting Liu Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket Synthetic and Systems Biotechnology Bifunctional terpene synthase Sesterterpene Carbocation transportation Density functional theory calculations Molecular dynamics simulations |
| title | Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket |
| title_full | Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket |
| title_fullStr | Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket |
| title_full_unstemmed | Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket |
| title_short | Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket |
| title_sort | expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation induced change in hydrogen bond network within the catalytic pocket |
| topic | Bifunctional terpene synthase Sesterterpene Carbocation transportation Density functional theory calculations Molecular dynamics simulations |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X24000413 |
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