Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme
Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in nature and possess a variety of biological activities. Up to date, only five fusicoccane-type diterpene synthases have been identified. Here, we identify a two-gene bio...
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2022-10-01
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| Series: | Beilstein Journal of Organic Chemistry |
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| Online Access: | https://doi.org/10.3762/bjoc.18.144 |
| _version_ | 1798043840219709440 |
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| author | Jia-Hua Huang Jian-Ming Lv Liang-Yan Xiao Qian Xu Fu-Long Lin Gao-Qian Wang Guo-Dong Chen Sheng-Ying Qin Dan Hu Hao Gao |
| author_facet | Jia-Hua Huang Jian-Ming Lv Liang-Yan Xiao Qian Xu Fu-Long Lin Gao-Qian Wang Guo-Dong Chen Sheng-Ying Qin Dan Hu Hao Gao |
| author_sort | Jia-Hua Huang |
| collection | DOAJ |
| description | Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in nature and possess a variety of biological activities. Up to date, only five fusicoccane-type diterpene synthases have been identified. Here, we identify a two-gene biosynthetic gene cluster containing a new fusicoccane-type diterpene synthase gene tadA and an associated cytochrome P450 gene tadB from Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D2O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione. |
| first_indexed | 2024-04-11T22:54:36Z |
| format | Article |
| id | doaj.art-7fe3321680eb4ac9a2cc0d4fb28cf678 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-04-11T22:54:36Z |
| publishDate | 2022-10-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-7fe3321680eb4ac9a2cc0d4fb28cf6782022-12-22T03:58:28ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972022-10-011811396140210.3762/bjoc.18.1441860-5397-18-144Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzymeJia-Hua Huang0Jian-Ming Lv1Liang-Yan Xiao2Qian Xu3Fu-Long Lin4Gao-Qian Wang5Guo-Dong Chen6Sheng-Ying Qin7Dan Hu8Hao Gao9Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Clinical Experimental Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China, Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in nature and possess a variety of biological activities. Up to date, only five fusicoccane-type diterpene synthases have been identified. Here, we identify a two-gene biosynthetic gene cluster containing a new fusicoccane-type diterpene synthase gene tadA and an associated cytochrome P450 gene tadB from Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D2O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione.https://doi.org/10.3762/bjoc.18.144cytochrome p450 enzymediterpene synthasegene clustergenome miningsite-directed mutagenesis |
| spellingShingle | Jia-Hua Huang Jian-Ming Lv Liang-Yan Xiao Qian Xu Fu-Long Lin Gao-Qian Wang Guo-Dong Chen Sheng-Ying Qin Dan Hu Hao Gao Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme Beilstein Journal of Organic Chemistry cytochrome p450 enzyme diterpene synthase gene cluster genome mining site-directed mutagenesis |
| title | Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme |
| title_full | Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme |
| title_fullStr | Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme |
| title_full_unstemmed | Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme |
| title_short | Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme |
| title_sort | characterization of a new fusicoccane type diterpene synthase and an associated p450 enzyme |
| topic | cytochrome p450 enzyme diterpene synthase gene cluster genome mining site-directed mutagenesis |
| url | https://doi.org/10.3762/bjoc.18.144 |
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