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[学术文献 ] Chemoenzymatic Synthesis and Protein Engineering Enable Efficient, Scalable Production of Teleocidin Derivatives 进入全文
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Monoterpenoid indole alkaloids (MIAs), a class of bioactive natural products, are highly valued in drug development for their unique pharmacological activities. Teleocidins, known for activating protein kinase C (PKC), are particularly promising but challenging to synthesize due to their structural complexity. Traditional methods often rely on heavy metals and yield low amounts, while biosynthetic approaches face efficiency issues. Our study developed an efficient chemoenzymatic route to produce 13 teleocidin B compounds and derivatives at scale. To overcome enzymatic reaction bottlenecks, we engineered the critical enzyme TleB by fusing a reductase module to create a self-sufficient P450 system, boosting indolactam V production to 868.8 mg L−1. Additionally, we established a dual-cell factory co-expressing engineered hMAT2A-TleD and TleB/TleC enzymes, enabling the first fully enzymatic synthesis of teleocidin B isomers with a total yield of 714.7 mg L−1. Chemical modifications further expanded the library with five novel indolactam V and two teleocidin A1 derivatives. Fermentation confirmed the recombinant Escherichia coli system's scalability, producing 430 mg indolactam V, 170 mg teleocidin A1, and 300 mg teleocidin B isomers. This work not only establishes a sustainable platform for teleocidin synthesis but also addresses efficiency and scalability challenges in complex natural product synthesis, paving the way for practical applications of bioactive compounds.
[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。
[前沿资讯 ] 魏茨曼科学研究所报道高效Kemp消除酶的完整计算设计 进入全文
科学网
魏茨曼科学研究所Sarel J. Fleishman研究团队报道了高效Kemp消除酶的完整计算设计。2025年6月18日，国际知名学术期刊《自然》发表了这一成果。 该研究团队提出了一个完全计算的工作流程，用于在TIM桶折叠中设计高效的酶，从天然蛋白质中提取主干片段，而无需通过突变文库筛选进行优化。三种Kemp消能设计的效率均大于 2,000 M−1 s−1。最有效的方法显示了来自任何天然蛋白质的140多个突变，包括一个新的活性位点。它具有高稳定性（大于85°C）和显著的催化效率（12,700 M−1 s−1）和速率（2.8s-1），比以前的计算设计高出两个数量级。 此外，设计一种在所有以前的Kemp消除设计中被认为是必不可少的残留物，可将效率提高到105 M−1 s−1，比率提高到30 s−1，实现与天然酶相当的催化参数，挑战基本的生物催化假设。通过克服设计方法上的限制，他们的策略使通过最小的实验努力就能编程出稳定、高效、全新的酶。 据了解，到目前为止，计算设计的酶表现出较低的催化速率，并且需要大量的实验优化才能达到与天然酶相似的活性水平。这些结果暴露了设计方法的局限性，并表明他们对生物催化基础知识的理解存在重大差距。
