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[学术文献 ] Mechanistic Insight into the Reproductive Toxicity of Trifloxystrobin in Male Sprague-Dawley Rats 进入全文
Environmental Science & Technology
Previous studies have demonstrated the reproductive toxicity of trifluorostrobin (TRI) in male organisms. However, the underlying mechanisms of TRI responsible for testicular damage and hormonal disruption remain elusive. This study elucidated the male reproductive toxicity of TRI at the molecular level under environmentally relevant concentrations and its associations with gut microbiota dysbiosis. The rats were administered TRI (1.5, 15, and 75 mg/kg of body weight/day) continuously via gavage for 90 days. Exposure to 15 mg/kg (below the no-observed adverse effect level (NOAEL) of 30 mg/kg) and 75 mg/kg TRI damaged testicular tissue, reduced sperm count, and lowered serum hormone and total cholesterol levels. Transcriptomics analysis combined with molecular docking simulations and cell proliferation assays showed that exposure to TRI led to testicular damage by inhibiting the expression of cholesterol receptor genes, which, in turn, disrupted steroid hormone biosynthesis. Furthermore, exposure to TRI resulted in a marked decline in the relative abundance of the probiotic bacteria. Consistently, significant reductions in the relative abundance of short-chain fatty acids (SCFAs), retinoic acids, and steroid hormones in the gut were observed. Additionally, a significant correlation was observed between the relative abundance of Parabacteroides and serum testosterone levels, a vital biomarker for reproductive toxicity monitoring. These findings shed light on the mode of action of TRI-induced male reproductive toxicity and highlight the link between testicular injury and gut microbiota.
[学术文献 ] Value-added biotransformation of agricultural byproducts by cellulolytic fungi: a review 进入全文
ENVIRONMENTAL SCIENCE & TECHNOLOGY
Agricultural byproducts generally contain abundant bioactive compounds (e.g., cellulose/hemicellulose, phenolic compounds (PCs), and dietary fibers (DFs)), but most of them are neglected and underutilized. Owing to the complicated and rigid structures of agricultural byproducts, a considerable amount of bioactive compounds are entrapped in the polymer matrix, impeding their further development and utilization. In recent years, the prominent performance of cellulolytic fungi to grow and degrade agricultural byproducts has been applied to achieve efficient biotransformation of byproducts to high-value compounds, which is a green and sustainable strategy for the reutilization of agricultural byproducts. This review comprehensively summarizes recent progress in the value-added biotransformation of agricultural byproducts by cellulolytic fungi, including (1) direct utilization of agricultural byproducts for biochemicals and bioethanol production via a consolidated bioprocessing, (2) recovery and biotransformation of bounded PCs from agricultural byproducts for higher bioactive properties, as well as (3) modification and conversion of insoluble DF from agricultural byproducts to produce functional soluble DF. The functional enzymes, potential mechanisms, and metabolic pathways involved are emphasized. Moreover, promising advantages and current bottlenecks using cellulolytic fungi have also been elucidated, shedding further perspectives for sustainable and efficient reutilization of agricultural byproducts by cellulolytic fungi.
[学术文献 ] Network for knowledge Organization (NEKO): An AI knowledge mining workflow for synthetic biology research 进入全文
Metabolic Engineering
Large language models (LLMs) can complete general scientific question-and-answer, yet they are constrained by their pretraining cut-off dates and lack the ability to provide specific, cited scientific knowledge. Here, we introduce Network for Knowledge Organization (NEKO), a workflow that uses LLM Qwen to extract knowledge through scientific literature text mining. When user inputs a keyword of interest, NEKO can generate knowledge graphs to link bioinformation entities and produce comprehensive summaries from PubMed search. NEKO significantly enhance LLM ability and has immediate applications in daily academic tasks such as education of young scientists, literature review, paper writing, experiment planning/troubleshooting, and new ideas/hypothesis generation. We exemplified this workflow's applicability through several case studies on yeast fermentation and cyanobacterial biorefinery. NEKO's output is more informative, specific, and actionable than GPT-4's zero-shot Q&A. NEKO offers flexible, lightweight local deployment options. NEKO democratizes artificial intelligence (AI) tools, making scientific foundation model more accessible to researchers without excessive computational power.
[学术文献 ] Computational Design-Enabled Divergent Modification of Monoterpene Synthases for Terpenoid Hyperproduction 进入全文
ACS CATALYSIS
Enzymes’catalytic promiscuity enables the alteration of product specificity via protein engineering; yet, harnessing this promiscuity to achieve desired catalytic reactions remains challenging. Here, we identified HCinS, a monoterpene synthase (MTPS) with a high efficiency and specificity for 1,8-cineole biosynthesis. Quantum mechanics/molecular mechanics (QM/MM) simulations, which were performed based on the resolved crystal structure of HCinS, revealed the mechanistic details of the biosynthetic cascade reactions. Guided by these insights, in silico HCinS variants were designed with fine-tuned transition-state energies and reaction microenvironments. Three variants (T111A, N135H, F236M), each with one amino acid substitution, exhibited high specificity in the production of monocyclic (R)-α-terpineol, (R)-limonene, and acyclic myrcene, respectively, maintaining over 55% efficiency of native HCinS. These designed HCinS variants surpassed naturally evolved isozymes in catalytic capacity and enabled yeast to achieve the highest microbial titer of each corresponding terpene. Furthermore, the single mutation of four functional equivalent amino acids in other four identified TPSs, respectively, resulted in the expected shifts on product specificity as HCinS variants. This research offers insights into the mechanisms controlling the TPS’s product promiscuity and highlights the universal applicability of computational design in reshaping the product specificity of TPSs, thereby paving innovative avenues for creating enzymes with applications in chemistry and synthetic biology.
[学术文献 ] Enhancing Manganese Peroxidase Innovations in Genetic Modification, Screening Processes, and Sustainable Agricultural Applications 进入全文
Journal of Agricultural and Food Chemistry
Manganese peroxidase (MnP), a vital extracellular enzyme for the degradation of lignin and other organic pollutants, has demonstrated immense potential for agricultural and environmental applications, including straw pretreatment, feed fermentation, mycotoxin degradation, and water treatment. However, current research remains in its exploratory phase, with naturally sourced MnP unable to meet industrial-scale demands and no mature commercial enzyme preparations available on the market. This comprehensive review innovatively constructs a framework for MnP research, probing into its molecular conformation and catalytic principles, while providing an overview of the advancements in high-throughput screening and In silco designing strategies. Specifically, this review focuses on the practical applications of MnP in sustainable agriculture, elaborating on its potential and challenges in straw resource utilization, efficient feed fermentation, mycotoxin control, and water quality improvement. Furthermore, this review summarizes the recent achievements in optimizing MnP activity through enzyme engineering techniques and discuss customized mutation strategies tailored to specific agricultural and environmental requirements, thereby laying a solid theoretical foundation and scientific basis for the industrial production and commercialization of MnP.
[学术文献 ] Metabolic engineering of Corynebacterium glutamicum: Unlocking its potential as a key cell factory platform for organic acid production 进入全文
Biotechnology Advances
Corynebacterium glutamicum, a well-studied industrial model microorganism, has garnered widespread attention due to its ability for producing amino acids with a long history. In recent years, research efforts have been increasingly focused on exploring its potential for producing various organic acids beyond amino acids. Organic acids, which are characterized by their acidic functional groups, have diverse applications across industries such as food, agriculture, pharmaceuticals, and biobased materials. Leveraging advancements in metabolic engineering and synthetic biology, the metabolic pathways of C. glutamicum have been broadened to facilitate the production of numerous high-value organic acids. This review summarizes the recent progress in metabolic engineering for the production of both amino acids and other organic acids by C. glutamicum. Notably, these acids include, amino acids (lysine, isoleucine, and phenylalanine), TCA cycle-derived organic acids (succinic acid, alpha-ketoglutaric acid), aromatic organic acids (protocatechuate, 4-amino-3-hydroxybenzoic acid, anthranilate, and para-coumaric acid), and other organic acids (itaconic acid and cis, cis-muconic acid).
