Critical Reviews in Biotechnology最新文献

Natural products and their derivatives have been important for treating diseases in humans, animals, and plants. However, discovering new structures from natural sources is still challenging. In recent years, artificial intelligence (AI) has greatly aided the discovery and development of natural products and drugs. AI facilitates to: connect genetic data to chemical structures or vice-versa, repurpose known natural products, predict metabolic pathways, and design and optimize metabolites biosynthesis. More recently, the emergence and improvement in neural networks such as deep learning and ensemble automated web based bioinformatics platforms have sped up the discovery process. Meanwhile, AI also improves the identification and structure elucidation of unknown compounds from raw data like mass spectrometry and nuclear magnetic resonance. This article reviews these AI-driven methods and tools, highlighting their practical applications and guide for efficient natural product discovery and drug development.

D-tagatose is a natural low-calorie rare sugar with nearly the same sweet taste as sucrose. It has nutritional and functional properties of great interest for health, such as anti-diabetes, anti-caries, anti-atherosclerosis, anti-hyperlipidemia, anti-aging, improvement of intestinal microflora, etc. The production of D-tagatose from D-galactose catalyzed by an alkali suffers from limited supplies of costly feedstock (i.e., lactose) and high manufacturing costs due to harsh reaction conditions, costly separation, as well as severe degradation and pollution. In this review, we briefly present the properties of D-tagatose and its physiological effects, review the recent advances in the biosynthesis of D-tagatose from inexpensive and abundant glucans (e.g., starch) and their derivatives (e.g., D-glucose and D-fructose) and from lactose, including both academic literature and industrial patents, as well as discuss its future challenges and opportunities. The biosynthesis of D-tagatose can be catalyzed by four types of biocatalysts: enzymes, whole-cells, microbial fermentation, and in vitro multi-enzyme molecular machines. The biomanufacturing of starchy D-tagatose catalyzed by multi-enzyme molecular machines could be the most promising approach because it not only makes D-tagatose from ample starch but also surpasses the equilibria of monosaccharide isomerization reactions (e.g., D-fructose-to-D-tagatose, D-galactose-to-D-tagatose). D-tagatose as a filler for a variety of food and drinks or a key component mixed with other sweeteners would become a predominant starch-derived sweetener and partially replace high-fructose corn sirup in the future.

Polymerase chain reaction (PCR) is a critical technology in nucleic acid detection and quantification. The PCR reaction requires thermal cycling the reaction mixture between two or more temperature stages for ∼30 cycles to achieve exponential amplification of the target DNA. Typically, the thermal cycling takes roughly an hour to finish and the large time consumption is a drawback for PCR. We review the various methods developed to reduce the thermal cycling time and build a rapid PCR. We group the methods to two approaches. The first approach is to increase the local heating/cooling power. The methods in this approach include contact heating, such as: heating resistors and Peltier pumps, and non-contact heating using air-blow, radiation on water and plasmonics. The other approach is to rapidly move the reaction mixture to a different temperature zone. Methods in this approach include: relocating the reaction vessel, continuous flow PCR using microfluidic chips, long tubes or oscillatory PCR scheme, and convective PCR. We analyze the advantages and challenges for each method used and the critical parameters to consider when evaluating the technologies. We review the technological advances and commercialization for each method. We also discuss the current challenges and future directions in building an effective and commercial rapid PCR, with the emphasis on sensitivity, portability and cost.

The global escalation in tuberculosis (TB) cases accompanied by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (M.tb) emphasizes the critical requirement for novel potent drugs. The M.tb demonstrates extraordinary adaptability, thriving in diverse conditions, and always finds itself in win-win situations regardless of whether the environment is favorable or unfavorable; no matter the magnitude of the challenge, it can endure and survive. This review aims to uncover the role of multiple stress sensors of M.tb that assist bacteria in remaining viable within the host for years against various physiological stresses offered by the host. M.tb is an exceptionally triumphant pathogen, primarily due to its adeptness in developing defense mechanisms against stressful situations. The recent advances emphasize the significance of M.tb stress sensors, including chaperones, proteases, transcription factors, riboswitches, inteins, etc., employed in responding to a spectrum of physiological stresses imposed by the host, encompassing surface stress, host immune responses, osmotic stress, oxidative and nitrosative stresses, cell envelope stress, environmental stress, reductive stress, and drug pressure. These sensors act as silent defenders orchestrating adaptive strategies, with limited comprehensive information in current literature, necessitating a focused review. The M.tb strategies utilizing these stress sensors to mitigate the impact of traumatic conditions demand attention to neutralize this pathogen effectively. Moreover, the intricacies of these stress sensors provide potential targets to design an effective TB drug using structure-based drug design against this formidable global health threat.

The convoluted relationships between plants, viruses, and arthropod vectors housing bacterial endosymbionts are pivotal in the spread of harmful plant viral diseases. Endosymbionts play key roles in: manipulating host responses, influencing insect resistance to pesticides, shaping insect evolution, and bolstering virus acquisition, retention, and transmission. This interplay presents an innovative approach for developing sustainable strategies to manage plant diseases. Recent progress in targeting specific endosymbionts through genetic modifications, biotechnological advancements, and RNA interference shows potential for curbing viral spread and disease progression. Additionally, employing synthetic biology techniques like CRISPR/Cas9 to engineer endosymbionts and disrupt crucial interactions necessary for viral transmission in arthropod vectors holds promise for effective control measures. In this review, these obligate and facultative bacterial cruxes have been discussed to elaborate on their mechanistic involvement in the regulation and/or inhibition of tripartite pathways of interactions. Furthermore, we provide an in-depth understanding of endosymbionts' synergistic and antagonistic effects on: insect biology, plant immunity, and virus acquisition and transmission. Finally, we point out open questions for future research and provide research directions concerning the deployment of genetically engineered symbionts to affect plant-virus-vector interactions for sustainable disease management. By addressing existing knowledge gaps and charting future research paths, a deeper comprehension of the role of endosymbionts in plant-virus-vector interactions can pave the way for innovative and successful disease management strategies. The exploration of antiviral therapies, paratransgenesis, and pathogen-blocking tactics using engineered endosymbionts introduces pioneering solutions for lessening the impact of plant viral diseases and green pest management.

Bioprocess industries aim to meet the increasing demand for product complexity by designing enhanced cellular and metabolic capabilities for the host. Monocultures, standard biomanufacturing workhorses, are often restricted in their capability to meet these demands, and the solution often involves the genetic modification of the host. Synthetic microbial communities are a promising alternative to monocultures because they exhibit division of labor, enabling efficient resource utilization and pathway modularity. This specialization minimizes metabolic burden and enhances robustness to perturbations, providing a competitive advantage. Despite this potential, their utilization in biotechnological or bioprocessing applications remains limited. The recent emergence of new and innovative community design tools and strategies, particularly those harnessing the division of labor, holds promise to change this outlook. Understanding the microbial interactions governing natural microbial communities can be used to identify complementary partners, informing synthetic community design. Therefore, we particularly consider engineering division of labor in synthetic microbial communities as a viable solution to accelerate progress in the field. This review presents the current understanding of how microbial interactions enable division of labor and how this information can be used to design synthetic microbial communities to perform tasks otherwise unfeasible to individual organisms. We then evaluate laboratory and formal modeling approaches specifically developed to: elucidate microbial community physiology, guide experimental design, and improve our understanding of complex community interactions assisting synthetic community design. By synthesizing these insights, we aim to present a comprehensive framework that advances the use of microbial communities in biomanufacturing applications.

Exploring the untapped potential of deep-sea microorganisms, particularly their cold-active enzymes, or psychrozymes, offers exciting possibilities for revolutionizing various aspects of the food processing industry. This review focuses on these enzymes, derived from the largely unexplored depths of the deep ocean, where microorganisms have developed unique adaptations to extreme conditions. Psychrozymes, as bioactive molecules, hold significant promise for food industry applications. However, despite their potential, the understanding and industrial utilization of psychrozymes remains limited. This review provides an in-depth analysis of how psychrozymes can: improve processing efficiency, enhance sensory qualities, extend product shelf life, and reduce energy consumption across the food production chain. We explore the cryodefense strategies and cold-adaptation mechanisms that support these enzymes, shedding light on the most extensively studied psychrozymes and assessing their journey from theoretical applications to practical use in food production. The key properties, such as stability, substrate specificity, and catalytic efficiency in cold environments, are also discussed. Although psychrozymes show considerable promise, their large-scale application in the food industry remains largely unexplored. This review emphasizes the need for further research to unlock the full potential of psychrozymes, encouraging their broader integration into the food sector to contribute to more sustainable food production processes.

Limiting animal experiments is essential for ethical issues and also because scientific evidence highlights the discrepancies between human and animal metabolism. This review aims to provide a critical discussion of the strengths and limitations of the most appropriate in vitro intestine model to answer complex research questions in pharmaceutical and nutraceutical fields. This review describes the components contributing to the definition of the gut barrier structure, from the outer mucus layer to the inner part of lamina propria, including endothelial and neuronal networks. We conclude that the main advantage of these co-culture models is their versatility since they are modulable systems in which each component can be added, changed, or removed to reproduce a specific physiological condition each time. Additionally, we compare intestinal organoid models and microfluidic systems with well-established co-culture models.

This comprehensive review aims to explore and consolidate the current knowledge on dendrobine, including its biological activities, molecular mechanisms of action, effects on various physiological processes, potential toxicity, and safety considerations, in order to unlock its full potential in various applications. Dendrobine has diverse biological effects, including anti-inflammatory, antioxidant, neuroprotective, immunomodulatory, and anticancer effects. Dendrobine also exerts neuroprotective effects by boosting neuronal survival, reducing neuroinflammation, and regulating neurotransmitter release. Dendrobine also has immunomodulatory effects that control immune cell function and modify immunological responses. Dendrobine also exhibits anticancer properties by decreasing tumor angiogenesis and metastasis, causing apoptosis in cancer cells, and inhibiting cancer cell growth. This review also discusses the idea of a circular economy to produce dendrobine, researching cutting-edge and sustainable methods that maximize resource efficiency and reduce environmental effects. Additionally, by supporting circular economy principles for sustainable production and outlining potential future study areas, this discovery will help maximize the use of dendrobine in a variety of applications while preserving its safety and the environment. Future dendrobine research should focus on advancing its application in personalized medicine, exploring green bioproduction methods, and ensuring ethical sourcing practices. An enhanced understanding of its molecular mechanisms and the potential for synergistic therapies could revolutionize healthcare, whereas sustainable production methods and conservation efforts could safeguard its ecological impact.

The alarming rise in bacterial infections including those caused by multidrug-resistant pathogens has garnered the attention of the scientific community, compelling them to explore as novel and effective alternatives to combat these infections. Moreover, the emerging viruses such as Influenza A virus subtype H1N1 (A/H1N1), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Ebolavirus, recent coronavirus (SARS-CoV-2), etc. also has a significant impact all over the world. Therefore, the management of all such infections without any side effects is one of the most important challenges for the scientific community. Hence, the development of novel and effective antimicrobial agents is a need of the hour. In this context, Curcuma longa, commonly known as turmeric, has been used as traditional medicine for centuries to manage and treat such infections. Its bioactive constituent, curcumin has garnered significant attention in medicine due to its multifunctional bioactivities. Apart from antimicrobial properties, it also possesses potent antioxidant and anti-inflammatory activities. However, available reports suggest that its low solubility, stability, and biocompatibility limit its use. Moreover, on the other hand, it has been reported that these limitations associated with the use of curcumin can be resolved by transforming it into its nano-form, specifically curcumin nanoparticles. Recent advancements have brought curcumin nanoparticles into the spotlight, showcasing superior properties and a broad spectrum of antimicrobial applications. In this review, we have mainly focused on antimicrobial potential of curcumin and nanocurcumin, mechanisms underpinning their antimicrobial actions. Moreover, other aspects of toxicity and safety guidelines for nano-based products have been also discussed.