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[学术文献 ] Advances of computational protein design: Principles, strategies and applications in nutrition and health 进入全文
Biotechnology Advances
Computational methods and AI technology have had a profound impact on protein design, significantly enhancing the ability to predict protein structures and create proteins with custom-tailored functions. With the help of computational methods, traditional protein design strategies such as directed evolution, fusion protein, and key subunit interface redesign show unprecedented progress in the design of various protein biomaterials such as nanocages, nanocarriers, antibodies, biocatalytic enzymes and inhibitory peptides. Strategies include physics-mediated design, which leverages the physical principles underlying protein structure and dynamics, and AI-mediated design, which employs machine learning techniques to generate and optimize protein configurations. Together, these approaches represent the cutting-edge methodologies in the rational design of novel proteins with desired functions. By using these approaches, novel protein molecules, assemblies, antibodies and responsive nanofibrils were constructed, which can be further applied in the field of nutrition and health.
[学术文献 ] Microbial and enzymatic strategies for aflatoxin control: Integrating intelligent detection and computational design 进入全文
Food Chemistry
Aflatoxins (AFs), potent carcinogenic mycotoxins, pose a major global threat to human health. This review offers an in-depth summary of microorganisms capable of degrading AFs, including bacteria, probiotics, and fungi, and highlights the key enzymes responsible for detoxification. We propose an integrated system combining smartphone-based detection, machine learning-driven enzyme discovery, and computationally optimized biocatalyst design for effective AFs mitigation. Microbial degraders facilitate aflatoxin B1 (AFB1) detoxification through extracellular enzymatic activity or cell surface adsorption mechanisms. Enzymes such as laccase, peroxidase, reductase, and lactonase effectively convert AFB1 into less toxic metabolites. However, industrial application of AFs-degrading enzymes remains constrained by their instability and insufficient efficiency. Emerging technologies, including machine learning-driven enzyme discovery and computer-aided protein engineering demonstrate significant potential for enhancing enzyme performance. This review highlights that integrating intelligent detection systems with computer-aided enzyme design offers a transformative framework for proactive AF control throughout food and feed supply chains.
[学术文献 ] Metabolic engineering of Bacillus subtilis for the production of active hemoglobins and myoglobins by improving heme supply 进入全文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Hemoglobins (Hb) and myoglobins (Mb) are important hemoproteins with broad applications in food and medicine. Microbial cell factory is a promising approach for the green and sustainable production of hemoproteins. However, current microbial hosts face the challenges of safety and insufficient heme supply. Here, we report a global regulation strategy, “push–restrain–pull–block,” to enhance heme supply for producing various active Hb and Mb in food-grade Bacillus subtilis. Initially, the insufficient supply of the precursor 5-aminolevulinate was overcome by relieving feedback inhibition and mitigating the negative effects of HemX on HemA. Next, HemD was identified as the primary uroporphyrinogen III synthase and self-assembled with HemC to minimize the formation of the uroporphyrinogen I by-product. Additionally, the coproporphyrin-dependent pathway was selected as the superior downstream route for heme synthesis, and crucial rate-limiting steps were subsequently enhanced. Moreover, heme consumption was blocked by eliminating protoheme IX farnesyltransferase. Finally, through the combination and fine-tuned expression of key genes, a 221-fold improvement of heme supply was achieved in the engineered strain. Using this stable prokaryotic chassis, we achieved production of 0.81, 0.82, 1.11, and 1.01 g L−1 of soybean Hb, clover Hb (C-Hb), bovine Mb (B-Mb), and porcine Mb, respectively, through fermentation, marking the highest reported titers in prokaryotic systems. These hemoproteins exhibit properties similar to natural standards. Furthermore, the synthesized C-Hb and B-Mb demonstrated superior effects for preparing plant-based meat analogs as colorants and flavoring agents. This work provides a universal platform for producing other high-value hemoproteins, promising future advancements in food processing and biocatalysis.
[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.
