化学
立体化学
选择性
玉米赤霉烯酮
催化三位一体
催化作用
基质(水族馆)
内酯
酶
水解
真菌毒素
活动站点
生物化学
食品科学
海洋学
地质学
作者
Zhongxia Xu,Weidong Liu,Chun‐Chi Chen,Qian Li,Jian‐Wen Huang,Tzu‐Ping Ko,Guizhi Liu,Wenting Liu,Wei Peng,Ya‐Shan Cheng,Yun Chen,Jian Jin,Huazhong Li,Yingying Zheng,Rey‐Ting Guo
标识
DOI:10.1021/acscatal.6b01826
摘要
The enzyme ZHD101 from Clonostachys rosea hydrolyzes and deactivates the mycotoxin zearalenone (ZEN) and its zearalenol (ZOL) derivatives. ZHD101 prefers ZEN to ZOL as its substrate, but ZOL, especially the α-form, shows higher estrogenic toxicity than ZEN. To enhance α-ZOL selectivity, we solved the complex structures of ZHD101 with both ZOLs and modified several lactone-surrounding residues. Among the mutants, V153H maintained activity for ZEN but showed a 3.7-fold increase in specific activity against α-ZOL, with an ∼2.7-fold reduction in substrate affinity but a 5.2-fold higher turnover rate. We then determined two V153H/ZOL complex structures. Here, the α-ZOL lactone ring is hydrogen-bonded to the H153 side chain, yielding a larger space for H242 to reconstitute the catalytic triad. In conclusion, structure-based engineering was successfully employed to improve the ZHD101 activity toward the more toxic α-ZOL, with great potential in further industrial applications.
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