INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xiabin Chen,Yun Zhang,Junsen Tong,Pengfei Ouyang,Xingyu Deng,Jie Zhang,Huan Liu,Yihui Hu,Weixuan Yao,Jiye Wang,Xia Wang,Shurong Hou,Jianzhuang Yao
Enzyme therapy for cocaine detoxification should break down both cocaine and its primary toxic metabolite, benzoylecgonine (BZE), which is also the main form of cocaine contaminant in the environment. An ideal BZE-metabolizing enzyme (BZEase) is expected to be highly efficient and selective in BZE hydrolysis. Here, BZEase4 was engineered from bacterial cocaine esterase (CocE) by our reactant state-based enzyme design theories (RED), which has a 34,977-fold improved substrate discrimination between BZE and the neurotransmitter acetylcholine (ACh), compared with wild-type CocE. Under the physiological concentrations of BZE and ACh, the reaction velocity of BZEase4 against BZE is 2.25 × 10 6 -fold higher than it against ACh, suggesting BZEase4 has extremely high substrate selectivity for BZE over ACh to minimize the potential cholinergic side-effects. This study provides additional evidence supporting the further development of BZEase4 toward a promising therapeutic for cocaine overdose, a potentially effective and eco-friendly enzymatic method for BZE degradation in the environment.
研究领域:
生物化学
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药物开发
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环境科学
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产品关联
DOI
PubMed
高影响因子
Catalysis Science & Technology
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2023
·Vol. 13
·期 20
·5880-5891
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IF 5
Jinling Xu,Haisheng Zhou,Jiaqi Xu,Ziyuan Wang,Zhonglang Yu,Zhe Wang,Hongyu Zhang,Haoran Yu,Jianping Wu,Lirong Yang
Nitrile hydratase (NHase), an excellent biocatalyst, has been widely used for the production of amides, but the exothermic hydration reaction leads to its rapid inactivation, hindering its industrial applications, which requires the thermostability of NHase to be enhanced. In this study, employing NHase from Bordetella petrii DSM 12804 (NHAB) as the object, a computational strategy using synergetic energy and correlated configuration for redesigning enzymes (SECURE) was proposed to prune the reasonable mutant library and assemble effective single mutations, thus maximizing the thermostability of NHAB. Among the mutants, the best variant, A6M/B4M, combined six mutations in its α-subunit (S30T, A71D, A74D, A78R, S81T, and A133P) and four mutations in its β-subunit (L25F, G27Y, N59P, and A173N), showing an increase in Tm by 13.2 °C, an 866.0-fold prolonged half-life at 50 °C, and an 11.2% increase in activity. Then, the catalytic efficiency dramatically increased to 249.5 g L−1 acrylamide in 5 batches compared with that of 166.5 g L−1 by the wild type in 3 batches. Finally, the synergistic effect on the mutant represented by an overall change in structure and newly formed intermolecular interactions through dynamic simulations accounted for the enhanced thermostability. Thus, SECURE was demonstrated to be practical for the redesign of multimeric NHase, which also provided guidance for computational thermostability engineering of other industrial biocatalysts.
研究领域:
生物化学
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生物技术
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计算生物学
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酶学
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产品关联
DOI
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
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2025
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IF 21.1
Da Wan,Yilei Zhang,Sizhen He,Huizhu Cai,Xue Zhang,Qi Hu,Hengpan Yang,Chuanxin He
The electrocatalytic NO 3 - reduction reaction (NO 3 - RR) proves the feasibility for the synthesis of NH 3 under mild conditions, yet it still faces challenges such as poor product selectivity and low reaction rates. Inspired by biological enzymes that exhibit both high selectivity and superior reaction rates, we designed an enzyme-mimetic catalyst for highly efficient NO 3 - RR. Specifically, mesoporous carbon nanofibers (CNFs) act as confined microenvironments for the enrichment of reactants, and the synergistic catalysis of Cu nanoclusters (Cu NCs) and Cu single atoms (Cu SAs) can match the complex reaction pathways of multiple intermediates and multiple proton/electron transfers. Consequently, the as-synthesized Cu NCs&SAs @CNFs catalyst achieves a remarkable NH 3 Faradaic efficiency (FE) of 97.23 % and a high yield rate of 31.45 mg h −1 cm −1 . Additionally, we employed the Cu NCs&SAs @CNFs as a cathode to assemble a Zn-NO 3 - battery, the system maintains a stable open circuit voltage of 1.36 V over 10 h continuous operation. This work combines the regulation of active sites and tuning of microenvironments, which might provide some insights for designing enzyme-mimicking catalysts in various electrocatalytic systems.
研究领域:
电催化
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材料科学
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纳米技术
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能量转换
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环境修复
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）