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[学术文献 ] A generalized platform for artificial intelligence-powered autonomous enzyme engineering 进入全文
Nature Communications
Proteins are the molecular machines of life with numerous applications in energy, health, and sustainability. However, engineering proteins with desired functions for practical applications remains slow, expensive, and specialist-dependent. Here we report a generally applicable platform for autonomous enzyme engineering that integrates machine learning and large language models with biofoundry automation to eliminate the need for human intervention, judgement, and domain expertise. Requiring only an input protein sequence and a quantifiable way to measure fitness, this automated platform can be applied to engineer a wide array of proteins. As a proof of concept, we engineer Arabidopsis thaliana halide methyltransferase (AtHMT) for a 90-fold improvement in substrate preference and 16-fold improvement in ethyltransferase activity, along with developing a Yersinia mollaretii phytase (YmPhytase) variant with 26-fold improvement in activity at neutral pH. This is accomplished in four rounds over 4 weeks, while requiring construction and characterization of fewer than 500 variants for each enzyme. This platform for autonomous experimentation paves the way for rapid advancements across diverse industries, from medicine and biotechnology to renewable energy and sustainable chemistry.
[学术文献 ] Iterative enhancement of cutinase thermostability by multiple strategies based on combined directed evolution and computationally assisted design 进入全文
Bioresource Technology
Cutinase exhibits versatile biocatalytic potential in polymer degradation, textile processing, and industrial biocatalysis, where enhancing the thermal stability under extreme conditions is essential for practical applications. To enhance the thermal stability of Humicola insolens cutinase (HiC), a combination of strategies approach integrating error-prone PCR, computational design, and machine learning were implemented. Through systematic iterative recombination, an octuple mutant (M8) was developed with thermal tolerance and preserved catalytic activity. The engineered mutant demonstrated exceptional stability enhancements, exhibiting 8110- and 3982-fold increases in half-life at 65 °C and 70 °C, respectively, compared with wild-type HiC. Differential scanning calorimetry revealed a 13.0 °C elevation in melting temperature (Tm), while thermal inactivation analysis showed a 26.2 °C improvement in T (temperature causing 50 % activity loss in 60 min). Notably, M8 retained full activity at standard assay temperature and exhibited a broad pH profile despite incorporating eight stabilizing mutations. Molecular dynamics simulations and structural analyses revealed that the redistribution of surface electrostatic charges and a more compact overall structure were key factors in enhancing thermal stability. In summary, this study established a framework for rational thermostabilization of cutinases while providing molecular level insights into thermal adaptation mechanisms, with methodological implications for α/β-hydrolase family enzyme optimization. The engineered HiC mutant present significant potential for industrial processes requiring high-temperature operations.
[学术文献 ] Synergic removal of Aflatoxin B1 in oily matrices by focusing on the peroxidase-like nanozymes-driven strategies: Mechanisms and intermediate toxicity, nutritional impact, advances and challenges 进入全文
Trends in Food Science & Technology
This review provides the recent progress on the AFB1 detoxification from oily matrices by focusing on the peroxidase-based nanozymes technologies and enzymatic-like mechanisms of reactive species in detail for the first time. Significantly, the superiority of enzymatic-like activity in capturing/detoxifying AFB1 from oily matrices, change in nutritional quality, organoleptic profiles, and physicochemical properties of oils, and mechanism of action are highlighted by a comparison with various edible oil remediation systems (i.e., physicochemical, physical, chemical, and biological). The peroxidase nanozyme–based technologies could be of primary importance in the remediation of AFB1 from oily matrices due to the unique merits of nanozymes (e.g., low-cost, size/surface-dependent properties, excellent efficiency and durability/stability, recoverability, biocompatibility, many capabilities to maintain the nutritional quality, and without require to any pre-treatment). Finally, this review aimed to provide several beneficial insights regarding safety, universality, finance, ecology, rapidity, selectivity, detoxification path, and toxicity/biological nature of transformed products in peroxidase-mimicking nanozyme technologies.
[学术文献 ] Promoting efficient synthesis and customization of sphingans based on metabolic engineering and synthetic biology strategies 进入全文
Carbohydrate Polymers
Sphingans are important exopolysaccharides due to their unique functional characteristics and potential application prospects in various fields. In recent years, the chemical structure, biosynthesis and function of sphingans have been studied extensively. With the development of metabolic engineering and synthetic biology, problems that restricting the production capacity and the design of sphingans, such as complex synthetic path and unclear research background of the wildtype strain, would be expected to be solved to some extent. This review describes the structure and biosynthetic pathways of different sphingans, analyzes the feasibility of obtaining high-performance sphingans-producing strains via classical mutagenesis combined with high-throughput screening techniques and chassis cells construction, and focuses on discussing how to efficiently synthesize and customize sphingans based on metabolic engineering and synthetic biology strategies. These strategies include using highly effective tools like genomic metabolic network models (GSMM) and CRISPR to regulate metabolic pathways, as well as customizing sphingans with different molecular weight through molecular weight regulation and controllable substituent modification based on genetic engineering. At last, the main challenges and prospects are discussed.
[学术文献 ] AI-driven de novo enzyme design: Strategies, applications, and future prospects 进入全文
Biotechnology Advances
Enzymes are indispensable for biological processes and diverse applications across industries. While top-down modification strategies, such as directed evolution, have achieved remarkable success in optimizing existing enzymes, bottom-up de novo enzyme design has emerged as a transformative approach for engineering novel enzymes with customized catalytic functions, independent of natural templates. Recent advancements in artificial intelligence (AI) and computational power have significantly accelerated this field, enabling breakthroughs in enzyme engineering. These technologies facilitate the rapid generation of enzyme structures and amino acid sequences optimized for specific functions, thereby enhancing design efficiency. They also support functional validation and activity optimization, improving the catalytic performance, stability, and robustness of de novo designed enzymes. This review highlights recent advancements in AI-driven de novo enzyme design, discusses strategies for validation and optimization, and examines the challenges and future prospects of integrating these technologies into enzyme development.
[前沿资讯 ] 光酶催化官能团远端手性中心的对映汇聚 进入全文
科学网
2025年6月24日，美国伊利诺伊大学香槟分校（University of Illinois Urbana-Champaign）赵惠民教授团队在Nature Catalysis期刊在线发表了题为“Photoenzymatic stereoablative enantioconvergence of γ-chiral oximes via hydrogen atom transfer”的研究成果。 该研究报道了一种基于光酶催化氢原子转移的对映汇聚策略，实现官能团远端的γ-手性碳氢键的立体选择性重构。由外消旋体合成对映纯的手性分子在药物、材料和天然产物合成中有广泛的应用前景。尽管传统的有机合成方法在官能团近端手性构建方面已取得显著进展，但对于远离官能团的碳氢键实现高效、对映选择性的构筑，仍是当前化学方法的难题。主要限制因素是官能团远端碳氢键的活性较低、空间位阻难以控制，以及存在复杂的副反应。相比之下，生物催化具备独特优势。酶以其高度结构化的活性位点，能够在温和条件下实现对底物的精确识别与空间调控，尤其在立体选择性转化中表现出色。近年来，借助定向进化与人工设计，许多天然的非光酶被成功“改造”以参与光诱导自由基反应，拓展了酶在非天然反应中的应用边界。 在该项研究中，赵惠民团队设计了一种结合光诱导单电子转移与氢原子转移（HAT）的催化体系，利用黄素依赖型烯还原酶（ERED）在蓝光照射下形成亚胺基自由基，诱发γ-位点的1,5-HAT实现手性信息的“消除”，随后通过酶活性位点控制的对映选择性HAT完成产物的手性重建，最终通过水解生成γ-手性酮产物。该策略突破了传统酶催化的空间限制，在实现反应远距立体控制的同时，避免了半量原料损耗，理论上可实现100%的对映体转化率。从机制上看，作者通过一系列实验和计算发现：R/S底物在该体系中具有相似的反应性；γ-手性中心的氢原子主要来源于还原态黄素（FMNH-）；存在亚胺基自由基直接从半醌态黄素（FMNsq）获得氢的副反应，和目标1,5-HAT构成竞争。 在此基础上，研究团队进一步引入多轮对映汇聚催化循环，有效富集优势构型产物，最高可实现最高97:3 e.r.与99%的产率。该方法适用于一系列含芳香基或杂环结构的γ-手性底物，展现出一定的底物适应性。该策略有望应用于药物合成、材料功能化及分子骨架改造等前沿领域，为发展绿色、精准的生物合成技术提供新的思路。
