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[前沿资讯 ] 蛋白质赖氨酸位点精准修饰新路径 进入全文
科学网
2025年9月25日，国科大杭州高等研究院张夏衡实验室与俞飚院士团队合作，在Chem期刊上发表了题为“Rewriting lysine reactivity: Lysine-targeted bioconjugation via biomimetic polarity reversal for diversified biomolecule modification”的研究论文。该研究报道了一种新型仿生氧化脱氨策略，实现了多肽和蛋白质上赖氨酸残基的位点选择性修饰。传统赖氨酸的修饰依赖于赖氨酸残基的亲核性，受其余天然氨基酸残基（如半胱氨酸、组氨酸等）亲核性的影响，之前报道的赖氨酸的修饰方法具有较多的限制。上述研究团队巧妙运用仿生策略，成功实现赖氨酸残基在原位形成具有亲电特性的醛中间体。该中间体能够精准且选择性地与多种携带不同官能团的亲核试剂发生反应进而实现定点赖氨酸修饰。该策略具有优异的生物兼容性和化学选择性，有效突破了传统赖氨酸修饰方法所面临的局限性。
[前沿资讯 ] 中国科学院天津工业生物技术研究所在甲醇脱氢酶的全酶组装机制研究方面取得新进展 进入全文
中国科学院天津工业生物技术研究所
二氧化碳（CO2）资源化利用是全球可持续发展面临的巨大挑战。利用可再生能源将CO2高效转化为甲醇再经生物转化合成众多化学品的杂合固碳方式已成为克服这一挑战的有效举措。然而，当前甲醇生物转化技术的发展仍受限于转化速率与转化率难以协同提升的瓶颈问题，其根源在于缺乏同时具备高能量效率和高催化速率的甲醇氧化还原酶。针对这一关键瓶颈，中国科学院天津工业生物技术研究所江会锋研究员带领的新酶设计研究团队聚焦于自然界中天然兼具优异的甲醇氧化能量效率和催化速率的吡咯喹啉醌（PQQ）依赖型甲醇脱氢酶（MDH），通过对其由14个基因组成的生物合成基因簇进行理性重构与优化，首次在国际上实现了该酶在模式工业微生物大肠杆菌中的异源合成与正确组装，一举攻克了其长期依赖天然宿主分离纯化的历史性难题。在此基础上，研究团队进一步采用基因缺失与蛋白组分分析相结合的策略，精准鉴定了9个参与MDH合成与组装的关键基因，并发现了一个介导辅因子PQQ与酶蛋白分子精确装配的分子伴侣MxaJ。利用冷冻电镜解析MxaJ与酶蛋白组成的蛋白复合体结构，发现MxaJ通过与酶蛋白PQQ结合口袋上方的loop区相互作用，从而使该口袋得以暴露，进而促进PQQ的结合。这一研究不仅揭示了MDH的生物合成过程及组装机制，更重要的是，为甲醇生物转化技术提供了高性能的“理想生物催化剂”。这一突破性进展将有力驱动甲醇生物转化技术的发展，加速其迈向规模化工业应用的进程。
[学术文献 ] A Polymeric Approach to Designing Semisynthetic Enzymes 进入全文
ACS Synthetic Biology
Incorporating synthetic chemicals into natural enzyme scaffolds to create semisynthetic enzymes is a promising strategy for achieving novel enzymatic functions. However, limitations such as low efficiency and a lack of control have hindered their industrial application. In this study, we propose a polymeric approach to designing semisynthetic enzymes by integrating ruthenium-containing polymers with the transaminase (ATA) scaffold via a “grafting from” copolymerization method. Initially, we combine noncatalytic proteins with polymers acting as dehydrogenases to convert acetophenone to (R)-1-phenylethanol with 99% conversion and 94% enantiomeric excess (ee). Furthermore, a polymeric semisynthetic ATA, referred to as “PolySemiATA,” is created by combining ATA and polymer catalysts using the same methodology. Remarkably, PolySemiATA not only retains the natural catalytic activity of enzymes but also enables an efficient one-pot cascade from (S)-1-phenylethylamine to (R)-1-phenylethanol with 99% conversion and 93% ee. Furthermore, PolySemiATA displays a significant advantage in recycling, surpassing the performance of mixtures composed of ATA and polymer catalysts. This study demonstrates the concept of a polymeric approach for designing semisynthetic enzymes, holding potential for producing high-value chemicals with various enzymes combined with different catalytic modular polymers to meet the demands of advanced synthesis.
[前沿资讯 ] 中国科学院天津工业生物技术研究所开发基于深度学习的密码子优化模型DeepCodon 进入全文
中国科学院天津工业生物技术研究所
近日，中国科学院天津工业生物技术研究所江会锋研究员带领的新酶设计研究团队在密码子优化研究方面取得重要进展。研究团队开发了一种基于深度学习的密码子优化模型DeepCodon。该模型在提升密码子偏好性的同时，尽可能保留功能相关的稀有密码子特征，为工程菌株的序列设计提供了新的思路。DeepCodon以人工智能学习密码子选择规律为基础，建立了从蛋白质到编码序列的“翻译映射”。在大规模序列数据训练的基础上，研究团队对高表达基因进行微调，使模型在生成合理密码子序列的同时能够兼顾高表达性能。进一步，DeepCodon引入条件概率策略，优先保护进化上保守、与功能相关的稀有密码子簇，从而避免传统方法中过度使用高频密码子所带来的翻译拥堵和错误折叠风险。在实验验证中，研究团队分别利用DeepCodon与传统方法优化了20个基因并在大肠杆菌中表达，结果显示9个DeepCodon优化的基因表达显著高于传统方法，10个基因与传统方法相当，仅1个低于传统方法，充分展示了该模型在实际应用中的潜力。目前，该工具主要面向大肠杆菌应用场景，并提供免费在线密码子优化服务：https://deepcodon.biodesign.ac.cn/。
[学术文献 ] Optimizing enzymatic oil extraction: critical roles of enzyme selection, process parameters, and synergistic effects on yield and quality 进入全文
Food Chemistry
Traditional plant oil extraction methods face challenges like low efficiency and pollution. In contrast, aqueous enzymatic extraction (AEE) offers advantages such as mild extraction conditions, no solvent residues, and sustainability, ensuring oil safety. The specificity of enzymes makes efficient oil extraction possible, requiring careful optimization of parameters such as enzyme selection, pH, temperature, solid-liquid ratio, enzyme concentration. This review explains how to enhance the yield and quality of oil through the synergistic effects between enzymes and these parameters. Conversely, inappropriate conditions reduce enzyme efficiency, cause oxidative reactions, and produce harmful substances, adversely affecting the flavor, color, and nutritional properties of the oil. Moreover, physical field auxiliary technology further improve enzyme permeability, boosting release rates, quality, and economic benefits. Future research should focus on cost reduction, energy efficiency, and by-product quality improvement. This review provides a theoretical framework for optimizing AEE processes and highlights its potential for sustainable oil extraction.
[学术文献 ] Bacterial spore surface display system for enzyme stabilization in food industry: Principles, applications and efficiency optimization strategies 进入全文
Trends in Food Science & Technology
Enzymes serve as green biological catalysts with irreplaceable roles in the food industry. However, free enzymes face several challenges, including structural instability, irreversible activity loss, and high production costs, which restrict their industrial implementation. While current enzyme immobilization technologies using magnetic nanoparticles, liposomes, and metal-organic frameworks show promise, they encounter critical bottlenecks such as mass transfer limitations, enzyme activity loss, and high preparation costs. Bacterial spore surface display systems (BSSDS) utilizing bacterial spores as carriers have emerged as a promising enzyme immobilization platform, offering enhanced stability. This review comprehensively analyzes sporulation and spore resistance mechanisms while systematically elucidating fundamental BSSDS principles. Both recombinant and non-recombinant system construction principles are examined, followed by a thorough assessment of current BSSDS applications in the food industry, including food safety, wastewater treatment, and food processing. Various optimization strategies for enhancing display efficiency are critically evaluated, and emerging trends in the field are discussed to provide insights for industrial-scale implementation. The recombinant system provides superior long-term stability and cost-effectiveness through reusability, which positions it as a promising candidate for the food industry. Through systematic optimization strategies, advancements have been achieved in display efficiency. These technological innovations establish BSSDS as an increasingly promising platform for industrial enzyme immobilization, delivering sustainable and cost-efficient biocatalytic solutions to the food industry. Future development efforts should focus on multi-enzyme synergistic display systems, intelligent responsive carriers for controllable enzyme regulation, and exploring novel anchoring proteins to further expand the scope and scale of displayable enzymes across food industry applications.
