Improving Theaflavin-3,3′-digallate Production Efficiency Optimization by Transition State Conformation of Polyphenol Oxidase
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Published:2023-04-30
Issue:9
Volume:28
Page:3831
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Huang Ying1, Gao Changzheng2, Song Wei3, Wei Wanqing4, Chen Xiulai4, Gao Cong4ORCID, Liu Jia4, Wu Jing3, Liu Liming14
Affiliation:
1. School of Food Engineering, Anhui Science and Technology University, Chuzhou 233100, China 2. Department of Cardiology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China 3. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China 4. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
Abstract
Theaflavins (TFs) are good for health because of their bioactivities. Enzymatic synthesis of TFs has garnered much attention; however, the source and activity of the enzymes needed limit their wide application. In this study, a microbial polyphenol oxidase from Bacillus megaterium was screened for the synthesis of theaflavin-3,3′-digallate (TFDG). Based on structural and mechanistic analyses of the enzyme, the O-O bond dissociation was identified as the rate-determining step. To address this issue, a transition state (TS) conformation optimization strategy was adopted to stabilize the spatial conformation of the O-O bond dissociation, which improved the catalytic efficiency of tyrosinase. Under the optimum transformation conditions of pH 4.0, temperature 25 °C, (−)-epigallocatechin gallate/epicatechin gallate molar ratio of 2:1, and time of 30 min, Mu4 (BmTyrV218A/R209S) produced 960.36 mg/L TFDG with a 44.22% conversion rate, which was 6.35-fold higher than that of the wild type. Thus, the method established has great potential in the synthesis of TFDG and other TFs.
Funder
Foundation for Innovative Research Groups of the National Natural Science Foundation of China Key R&D Program of Jiangsu Province National Natural Science Foundation of China Fundamental Research Funds for the Central Universities Program for Young Talents in China
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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