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[学术文献 ] Impact of probiotics, prebiotics, and synbiotics on digestive enzymes, oxidative stress, and antioxidant defense in fish farming: current insights and future perspectives 进入全文
Frontiers in Marine Science
There has been a surge of research in the aquaculture industry investigating probiotic, prebiotic, and synbiotic interventions on the physiological mechanisms of fish, specifically digestive enzymes, oxidative stress, and antioxidant defense. In fish, probiotics have been shown to improve nutrient utilization and growth performance by stimulating digestive enzymes. Meanwhile, probiotics, prebiotics and synbiotics have also been studied for their ability to modulate oxidative stress and antioxidant defense mechanisms in fish, highlighting their multifaceted health benefits. This review identified current trends, research gaps, and future considerations in this evolving field. Although promising findings have been made, a significant research gap exists in understanding the specific role of probiotics prebiotics, and synbiotics in modulating digestive enzymes, oxidative stress, and antioxidant defense systems in a variety of fish species. As this study investigate into the existing body of literature, it becomes evident that while certain aspects of these interactions have been elucidated, a nuanced and comprehensive understanding still needs to be discovered. The variations in experimental design, species-specific responses, and the lack of standardized methodologies contribute to the complexity of the field. Digestive physiology and antioxidant defense mechanisms vary among different fish species, so future research should focus on species-specific responses to probiotic, prebiotic, and synbiotic formulations. It will also be possible to establish robust correlations between dietary interventions and observed effects through a systematic experimental design and methodology approach. Accordingly, further research is needed to understand the interactions between probiotics, prebiotics, and synbiotics in fish and digestive enzymes, oxidative stress, and antioxidant defense. Identifying research gaps and adopting standardized methodologies can help develop tailored strategies to optimize aquaculture fish health and growth performance.
[学术文献 ] Unlocking the potential of enzyme engineering via rational computational design strategies 进入全文
Biotechnology Advances
Enzymes play a pivotal role in various industries by enabling efficient, eco-friendly, and sustainable chemical processes. However, the low turnover rates and poor substrate selectivity of enzymes limit their large-scale applications. Rational computational enzyme design, facilitated by computational algorithms, offers a more targeted and less labor-intensive approach. There has been notable advancement in employing rational computational protein engineering strategies to overcome these issues, it has not been comprehensively reviewed so far. This article reviews recent developments in rational computational enzyme design, categorizing them into three types: structure-based, sequence-based, and data-driven machine learning computational design. Case studies are presented to demonstrate successful enhancements in catalytic activity, stability, and substrate selectivity. Lastly, the article provides a thorough analysis of these approaches, highlights existing challenges and potential solutions, and offers insights into future development directions.
[学术文献 ] Engineered polymer nanoparticles as artificial chaperones facilitating the selective refolding of denatured enzymes 进入全文
PNAS
Molecular chaperones assist in protein refolding by selectively binding to proteins in their nonnative states. Despite progress in creating artificial chaperones, these designs often have a limited range of substrates they can work with. In this paper, we present molecularly imprinted flexible polymer nanoparticles (nanoMIPs) designed as customizable biomimetic chaperones. We used model proteins such as cytochrome c, laccase, and lipase to screen polymeric monomers and identify the most effective formulations, offering tunable charge and hydrophobic properties. Utilizing a dispersed phase imprinting approach, we employed magnetic beads modified with destabilized whole-protein as solid-phase templates. This process involves medium exchange facilitated by magnetic pulldowns, resulting in the synthesis of nanoMIPs featuring imprinted sites that effectively mimic chaperone cavities. These nanoMIPs were able to selectively refold denatured enzymes, achieving up to 86.7% recovery of their activity, significantly outperforming control samples. Mechanistic studies confirmed that nanoMIPs preferentially bind denatured rather than native enzymes, mimicking natural chaperone interactions. Multifaceted analyses support the functionality of nanoMIPs, which emulate the protective roles of chaperones by selectively engaging with denatured proteins to inhibit aggregation and facilitate refolding. This approach shows promise for widespread use in protein recovery within biocatalysis and biomedicine.
[学术文献 ] Microbial production of sulfur-containing amino acids using metabolically engineered Escherichia coli 进入全文
BIOTECHNOLOGY ADVANCES
L-Cysteine and L-methionine, as the only two sulfur-containing amino acids among the canonical 20 amino acids, possess distinct characteristics and find wide-ranging industrial applications. The use of different organisms for fermentative production of L-cysteine and L-methionine is gaining increasing attention, with Escherichia coli being extensively studied as the preferred strain. This preference is due to its ability to grow rapidly in costeffective media, its robustness for industrial processes, the well-characterized metabolism, and the availability of molecular tools for genetic engineering. This review focuses on the genetic and molecular mechanisms involved in the production of these sulfur-containing amino acids in E. coli. Additionally, we systematically summarize the metabolic engineering strategies employed to enhance their production, including the identification of new targets, modulation of metabolic fluxes, modification of transport systems, dynamic regulation strategies, and optimization of fermentation conditions. The strategies and design principles discussed in this review hold the potential to facilitate the development of strain and process engineering for direct fermentation of sulfur-containing amino acids.
[学术文献 ] A systematic analysis of regression models for protein engineering 进入全文
Plos Computational Biology
To optimize proteins for particular traits holds great promise for industrial and pharmaceutical purposes. Machine Learning is increasingly applied in this field to predict properties of proteins, thereby guiding the experimental optimization process. A natural question is: How much progress are we making with such predictions, and how important is the choice of regressor and representation? In this paper, we demonstrate that different assessment criteria for regressor performance can lead to dramatically different conclusions, depending on the choice of metric, and how one defines generalization. We highlight the fundamental issues of sample bias in typical regression scenarios and how this can lead to misleading conclusions about regressor performance. Finally, we make the case for the importance of calibrated uncertainty in this domain. Supervised machine learning is increasingly used to predict the function and properties of proteins. The performance obtained with these methods relies on a multitude of factors including how data is represented, how observations are distributed, how training is conducted, and how performance is measured. In this paper, we systematically assess the importance of these different components in a protein regression pipeline. We discuss the benefits of using representations extracted from protein language models, the impact of the choice of regression algorithm, and the role of uncertainty. Finally, to avoid misleading performance claims, we stress the need for carefully aligning the train/test setup to reflect the setting in which the prediction algorithm will ultimately be applied.
[学术文献 ] Paternal microbiome perturbations impact offspring fitness 进入全文
Nature
The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks 1-4 . Environmental factors that unbalance gut microbial ecosystems can therefore shape physiological and disease-associated responses across somatic tissues 5-9 . However, the systemic impact of the gut microbiome on the germline-and consequently on the F1 offspring it gives rise to-is unexplored 10 . Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory 'gut-germline axis' in males, which is sensitive to environmental exposures and programmes offspring fitness through impacting placenta function. Disturbances in the gut microbiota of male mice manifest as fitness defects in their offspring by affecting plancenta function, revealing a paternal gut-germline axis.
