Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides
Anemarrhena asphodeloides is an immensely popular medicinal herb in China, which contains an abundant of mangiferin. As an important bioactive xanthone C-glycoside, mangiferin possesses a variety of pharmacological activities and is derived from the cyclization reaction of a benzophenone C-glycoside...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-03-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X22000035 |
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| author | Jia Huang Yaru She Jingyang Yue Yidu Chen Yu Li Jing Li Yonger Hu Deying Yang Jiabo Chen Lu Yang Zhongqiu Liu Ruibo Wu Pengfei Jin Lixin Duan |
| author_facet | Jia Huang Yaru She Jingyang Yue Yidu Chen Yu Li Jing Li Yonger Hu Deying Yang Jiabo Chen Lu Yang Zhongqiu Liu Ruibo Wu Pengfei Jin Lixin Duan |
| author_sort | Jia Huang |
| collection | DOAJ |
| description | Anemarrhena asphodeloides is an immensely popular medicinal herb in China, which contains an abundant of mangiferin. As an important bioactive xanthone C-glycoside, mangiferin possesses a variety of pharmacological activities and is derived from the cyclization reaction of a benzophenone C-glycoside (maclurin). Biosynthetically, C-glycosyltransferases are critical for the formation of benzophenone C-glycosides. However, the benzophenone C-glycosyltransferases from Anemarrhena asphodeloides have not been discovered. Herein, a promiscuous C-glycosyltransferase (AaCGT) was identified from Anemarrhena asphodeloides. It was able to catalyze efficiently mono-C-glycosylation of benzophenone, together with di-C-glycosylation of dihydrochalcone. It also exhibited the weak O-glycosylation or potent S-glycosylation capacities toward 12 other types of flavonoid scaffolds and a simple aromatic compound with –SH group. Homology modeling and mutagenesis experiments revealed that the glycosylation reaction of AaCGT was initiated by the conserved residue H23 as the catalytic base. Three critical residues H356, W359 and D380 were involved in the recognition of sugar donor through hydrogen-bonding interactions. In particular, the double mutant of F94W/L378M led to an unexpected enzymatic conversion of mono-C- to di-C-glycosylation. This study highlights the important value of AaCGT as a potential biocatalyst for efficiently synthesizing high-value C-glycosides. |
| first_indexed | 2024-04-24T08:43:55Z |
| format | Article |
| id | doaj.art-0a31d116e8e64e48be6b85878c0970eb |
| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T08:43:55Z |
| publishDate | 2022-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-0a31d116e8e64e48be6b85878c0970eb2024-04-16T14:11:40ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2022-03-0171621630Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloidesJia Huang0Yaru She1Jingyang Yue2Yidu Chen3Yu Li4Jing Li5Yonger Hu6Deying Yang7Jiabo Chen8Lu Yang9Zhongqiu Liu10Ruibo Wu11Pengfei Jin12Lixin Duan13Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR ChinaJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China; Corresponding author.Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR ChinaDepartment of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing, 100730, PR China; Corresponding author.Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China; Corresponding author.Anemarrhena asphodeloides is an immensely popular medicinal herb in China, which contains an abundant of mangiferin. As an important bioactive xanthone C-glycoside, mangiferin possesses a variety of pharmacological activities and is derived from the cyclization reaction of a benzophenone C-glycoside (maclurin). Biosynthetically, C-glycosyltransferases are critical for the formation of benzophenone C-glycosides. However, the benzophenone C-glycosyltransferases from Anemarrhena asphodeloides have not been discovered. Herein, a promiscuous C-glycosyltransferase (AaCGT) was identified from Anemarrhena asphodeloides. It was able to catalyze efficiently mono-C-glycosylation of benzophenone, together with di-C-glycosylation of dihydrochalcone. It also exhibited the weak O-glycosylation or potent S-glycosylation capacities toward 12 other types of flavonoid scaffolds and a simple aromatic compound with –SH group. Homology modeling and mutagenesis experiments revealed that the glycosylation reaction of AaCGT was initiated by the conserved residue H23 as the catalytic base. Three critical residues H356, W359 and D380 were involved in the recognition of sugar donor through hydrogen-bonding interactions. In particular, the double mutant of F94W/L378M led to an unexpected enzymatic conversion of mono-C- to di-C-glycosylation. This study highlights the important value of AaCGT as a potential biocatalyst for efficiently synthesizing high-value C-glycosides.http://www.sciencedirect.com/science/article/pii/S2405805X22000035C-glycosidesAnemarrhena asphodeloidesC-glycosyltransferasesBenzophenoneActive sites |
| spellingShingle | Jia Huang Yaru She Jingyang Yue Yidu Chen Yu Li Jing Li Yonger Hu Deying Yang Jiabo Chen Lu Yang Zhongqiu Liu Ruibo Wu Pengfei Jin Lixin Duan Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides Synthetic and Systems Biotechnology C-glycosides Anemarrhena asphodeloides C-glycosyltransferases Benzophenone Active sites |
| title | Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides |
| title_full | Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides |
| title_fullStr | Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides |
| title_full_unstemmed | Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides |
| title_short | Exploring the catalytic function and active sites of a novel C-glycosyltransferase from Anemarrhena asphodeloides |
| title_sort | exploring the catalytic function and active sites of a novel c glycosyltransferase from anemarrhena asphodeloides |
| topic | C-glycosides Anemarrhena asphodeloides C-glycosyltransferases Benzophenone Active sites |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X22000035 |
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