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[学术文献 ] Two different types of hydrolases co-degrade ochratoxin A in a highly efficient degradation strain Lysobacter sp. CW239 进入全文
Journal of Hazardous Materials
Ochratoxin A (OTA) is a toxic secondary metabolite that widely contaminates agro-products and poses a significant dietary risk to human health. Previously, a carboxypeptidase CP4 was characterized for OTA degradation in Lysobacter sp. CW239, but the degradation activity was much lower than its host strain CW239. In this study, an amidohydrolase ADH2 was screened for OTA hydrolysis in this strain. The result showed that 50 μg/L OTA was completely degraded by 1.0 μg/mL rADH2 within 5 min, indicating ultra-efficient activity. Meanwhile, the two hydrolases (i.e., CP4 and ADH2) in the strain CW239 showed the same degradation manner, which transformed the OTA to ochratoxin α (OTα) and l-β-phenylalanine. Gene mutants (Δcp4, Δadh2 and Δcp4-adh2) testing result showed that OTA was co-degraded by carboxypeptidase CP4 and amidohydrolase ADH2, and the two hydrolases are sole agents in strain CW239 for OTA degradation. Hereinto, the ADH2 was the overwhelming efficient hydrolase, and the two types of hydrolases co-degraded OTA in CW239 by synergistic effect. The results of this study are highly significant to ochratoxin A contamination control during agro-products production and postharvest.
[学术文献 ] TemBERTure: advancing protein thermostability prediction with deep learning and attention mechanisms 进入全文
Bioinformatics Advances
Motivation Understanding protein thermostability is essential for numerous biotechnological applications, but traditional experimental methods are time-consuming, expensive, and error-prone. Recently, deep learning (DL) techniques from natural language processing (NLP) was extended to the field of biology, since the primary sequence of proteins can be viewed as a string of amino acids that follow a physicochemical grammar. Results In this study, we developed TemBERTure, a DL framework that predicts thermostability class and melting temperature from protein sequences. Our findings emphasize the importance of data diversity for training robust models, especially by including sequences from a wider range of organisms. Additionally, we suggest using attention scores from Deep Learning models to gain deeper insights into protein thermostability. Analyzing these scores in conjunction with the 3D protein structure can enhance understanding of the complex interactions among amino acid properties, their positioning, and the surrounding microenvironment. By addressing the limitations of current prediction methods and introducing new exploration avenues, this research paves the way for more accurate and informative protein thermostability predictions, ultimately accelerating advancements in protein engineering.
[学术文献 ] Chemoenzymatic Synthesis of Fluorinated Mycocyclosin Enabled by the Engineered Cytochrome P450-Catalyzed Biaryl Coupling Reaction 进入全文
Journal of the American Chemical Society
Installing fluorine atoms onto natural products holds great promise for the generation of fluorinated molecules with improved or novel pharmacological properties. The enzymatic oxidative carbon–carbon coupling reaction represents a straightforward strategy for synthesizing biaryl architectures, but the exploration of this method for producing fluorine-substituted derivatives of natural products remains elusive. Here, in this study, we report the protein engineering of cytochrome P450 from Mycobacterium tuberculosis (MtCYP121) for the construction of a series of new-to-nature fluorine-substituted Mycocyclosin derivatives. This protocol takes advantage of a “hybrid” chemoenzymatic procedure consisting of tyrosine phenol lyase-catalyzed fluorotyrosine preparation from commercially available fluorophenols, intermolecular chemical condensation to give cyclodityrosines, and an engineered MtCYP121-catalyzed intramolecular biphenol coupling reaction to complete the strained macrocyclic structure. Computational mechanistic studies reveal that MtCYP121 employs Cpd I to abstract a hydrogen atom from the proximal phenolic hydroxyl group of the substrate to trigger the reaction. Then, conformational change makes the two phenolic hydroxyl groups close enough to undergo intramolecular hydrogen atom transfer with the assistance of a pocket water molecule. The final diradical coupling process completes the intramolecular C–C bond formation. The efficiency of the biaryl coupling reaction was found to be influenced by various fluorine substitutions, primarily due to the presence of distinct binding conformations.
[学术文献 ] Biodegradation Characteristics and Mechanism of Aflatoxin B1 by Bacillus amyloliquefaciens from Enzymatic and Multiomics Perspectives 进入全文
Journal of Agricultural and Food Chemistry
Aflatoxin B1 (AFB1), a mycotoxin and natural carcinogen, commonly contaminates cereals and animal feeds, posing serious health risks to human and animal. In this study, Bacillus amyloliquefaciens ZG08 isolated from kimchi could effectively remove 80.93% of AFB1 within 72 h at 37 °C and pH 7.0. Metabolome and transcriptome analysis showed that metabolic processes including glycerophospholipid metabolism and amino acid metabolism were most affected in B. amyloliquefaciens ZG08 exposed to AFB1. The adaptation mechanism likely involved activation of the thioredoxin system to restore intracellular redox equilibrium. The key genes, tpx and gldA, overexpressed in Escherichia coli BL21, achieved degradation rates of 60.15% and 47.16% for 100 μg/kg AFB1 under optimal conditions of 37 °C and pH 8.0 and 45 °C and pH 7.0, respectively. The degradation products, identified as AFD1, were less cytotoxic than AFB1 in HepG2 cells. These findings suggest potential strategies for utilizing probiotics and engineered enzymes in AFB1 detoxification.
[前沿资讯 ] Organic nanozymes have broad applications from food and agriculture to biomedicine 进入全文
Eurekalert
纳米酶是一种微小的工程物质，可以模仿天然酶的催化特性，在生物医学、化学工程和环境应用领域有多种用途。它们通常由无机材料制成，包括金属基元素，由于其毒性和高生产成本，使其不适合用于许多用途。有机纳米酶部分克服了这些问题，并具有更广泛的应用潜力，包括食品和农业，但它们仍处于发展的早期阶段。 伊利诺伊大学香槟分校的一篇新论文概述了有机纳米酶的现状及其未来的潜力。在论文中，研究人员根据用于制造有机纳米酶的有机材料，确定了四种主要类型的有机纳米酶，包括聚合物、生物大分子（主要是纤维素）、有机化合物以及 DNA 和肽等生物材料。他们概述了每种类型的化学结构、成分、功能和催化活性，为其他科学家提供了基本信息。他们还说明了从农业、食品和环境到生物医药的相应应用。 Kamruzzaman 指出，无机纳米酶起源于生物医学领域，约 80% 的研究都发生在该领域。例如，它们用于诊断医学、成像、治疗和生物传感。然而，人们担心其固有毒性及其在治疗应用中对细胞活力的影响。有机纳米酶可以缓解这些担忧，并将其应用扩展到食品和农业领域。在之前的一项研究中，Kamruzzaman 和 Lee 率先使用以农业为中心的有机纳米酶，并结合分子传感工具，可以检测食品中是否存在农业农药。最终目标是创建一个简单的测试套件，人们可以在任何地方使用，并使用手机应用程序扫描结果，以获得指示食品中农药浓度的颜色读数。还推出了几种由可持续材料制成的额外有机纳米酶，并且正在开发更先进的分子传感系统。 Kamruzzaman 说：“有机纳米酶与无机纳米酶相比具有许多优势，但它们仍处于早期开发阶段，要将它们应用于食品和农业领域，我们还需要克服许多挑战。”一个障碍是适合生产的有机材料种类有限。研究人员指出，脂质或氨基酸是未来原型的有前途的材料，可以在开发下一代纳米酶方面发挥关键作用。
[前沿资讯 ] 黄曲霉毒素生物合成抑制剂研发获新进展 进入全文
科学网
广东省农业科学院农业生物基因研究中心作物品质控制与多组学技术创新团队（筹）与甘肃农业大学资环学院教授张军团队合作，在黄曲霉毒素生物合成抑制剂研发方面取得新进展，建立一套从分子原子水平理解黄曲霉毒素合成关键酶功能机制到高效筛选抑制剂的方法体系。相关成果近日在线发表于《微生物学前沿》（Frontiers in Microbiology）。研究人员通过基于人工智能的结构建模和微秒级分子动力学模拟，获得了对AflG及其结合底物AVN复合物三维结构的新见解。随后通过对超过130万个化合物进行高通量虚拟筛选，确定了具有良好预测对接得分的化合物子集。根据结合自由能计算对这些化合物进行排序，并进一步通过微秒级分子动力学模拟和黄曲霉菌外施实验评估其对黄曲霉毒素合成的调控作用，结果发现了两种新型化合物能够显著抑制黄曲霉毒素的生物合成。该研究建立了一套从分子原子水平理解黄曲霉毒素合成关键酶功能机制到高效筛选抑制剂的方法体系，为解决黄曲霉毒素污染问题提供了新的思路，对农产品中毒素污染的源头防控技术开发具有重要的理论意义和潜在应用价值。
