Critical Reviews in Biotechnology最新文献

5-Aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid essential for synthesizing tetrapyrrole compounds, including heme, chlorophyll, cytochrome, and vitamin B12. As a plant growth regulator, 5-ALA is extensively used in agriculture to enhance crop yield and quality. The complexity and low yield of chemical synthesis methods have led to significant interest in the microbial synthesis of 5-ALA. Advanced strategies, including the: enhancement of precursor and cofactor supply, compartmentalization of key enzymes, product transporters engineering, by-product formation reduction, and biosensor-based dynamic regulation, have been implemented in bacteria for 5-ALA production, significantly advancing its industrialization. This article offers a comprehensive review of recent developments in 5-ALA production using engineered bacteria and presents new insights to propel the field forward.

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.

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.

Recently, bioactive peptides, from natural resources, have attracted remarkable attention as nutraceutical treasures and the health benefits of their consumption have extensively been studied. Therapies based on bioactive peptides have been recognized as an innovative and promising alternative method for dangerous diseases such as cancer. Indeed, there has been enormous interest in nutraceuticals and bioactive-based chemopreventive molecules as a potential opportunity to manage chronic diseases, including cancer at different stages, rather than the traditionally used therapies. The relative safety and efficacy of these peptides in targeting only the tumor cells without affecting the normal cells make them attractive alternatives to existing pharmaceuticals for the treatment, management, and prevention of cancer, being able to act as potential physiological modulators of metabolism during their intestinal digestion. Novel bioactive peptides derived from food sources can be beneficial as anticancer nutraceuticals and provide a basis for the pharmaceutical development of food-derived bioactive peptides. Bioactive peptides can be generated through different protein hydrolysis methods and purified using advanced chromatographic techniques. Moreover, establishing bioactive peptides' efficacy and mechanism of action can provide alternative methods for cancer prevention and management. Most of the research on anticancer peptides is carried out on cell lines with very limited research being investigated in animal models or human clinical models. In this context, this review article comprehensively discusses anticancer peptides': production, isolation, therapeutic strategies, mechanism of action, and application in cancer therapy.

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.

Nicotinamide mononucleotide (NMN) presents significant therapeutic potential against aging-related conditions, such as Alzheimer's disease, due to its consistent and strong pharmacological effects. Aside from its anti-aging effect, NMN is also an emerging noncanonical cofactor for orthogonal metabolic pathways in the field of biomanufacturing. This has significant advantages in the field of metabolic engineering, allowing cells to produce unnatural chemicals without disrupting the natural cellular processes. NMN is produced through both the chemical and biological methods, with the latter being more environmentally sustainable. The primary biological production pathway centers on the enzyme nicotinamide phosphoribosyltransferase, which transforms nicotinamide and phosphoribosyl pyrophosphate to NMN. Efforts to increase NMN production have been explored in microorganisms, such as: Escherichia coli, Bacillus subtilis, and yeast, serving as biocatalysts, by rewiring their metabolic processes. Although most researchers are focusing on genetically and metabolically manipulating microorganisms to act as biocatalysts, a growing number of studies on cell-free synthesis are emerging as a promising strategy for producing NMN. This review explores the different biological production techniques of NMN employing microorganisms. This article, in particular, is essential to those who are working on NMN production using microbial strain engineering and cell-free systems.

Muconic acid (MA) is a valuable dicarboxylic acid with three isomers that are extensively utilized in textile and chemical industries. Traditionally, the chemical synthesis of MA consumes nonrenewable petrochemical raw materials and causes significant environmental problems. With the rapid increase in demand for MA, eco-friendly biosynthetic technologies with renewable sources are becoming ideal alternative solutions. This paper systematically reviews recent advances in the biosynthesis of MA isomers, describing not only the mechanism for MA biosynthesis in different microorganisms, including wild and engineered strains, but also focuses on MA production from various renewable resources, especially lignin hydrolysate and lignin-derived aromatics hydrocarbons, such as: benzoic acid, isoeugenol, vanillic acid and phenol. Moreover, cis,cis-muconic acid production from xylose, PET, methane, and glycerol are discussed in detail, providing a much broader substrate spectra and further possibilities for MA large scale industrialization economically. Challenges facing biosynthesis of cis, trans muconic acid and trans, trans muconic acid are discussed finally.

The C1 resource is widely considered because of its abundance and affordability. In the context of extensive utilization of C1 resources by methylotrophic microorganisms, especially for methanol, formaldehyde is an important intermediate metabolite that is at the crossroads of assimilation and dissimilation pathways. However, formaldehyde is an exceedingly reactive compound that can form covalent cross-linked complexes with amine and thiol groups in cells, which causes irreversible damage to the organism. Thus, it is important to balance the intensity of the assimilation and dissimilation pathways of formaldehyde, which can avoid formaldehyde toxicity and improve the full utilization of C1 resources. This review details the source of endogenous formaldehyde and its toxicity mechanism, explaining the harm of excessive accumulation of formaldehyde to metabolism. Importantly, the self-detoxification and various feasible strategies to mitigate formaldehyde toxicity are discussed and proposed. These strategies are meant to help appropriately handle formaldehyde toxicity and accelerate the effective use of C1 resources.

Fungal diseases threaten the forest ecosystem, impacting tree health, productivity, and biodiversity. Conventional approaches to combating diseases, such as biological control or fungicides, often reach limits regarding efficacy, resistance, non-target organisms, and environmental impact, enforcing alternative approaches. From an environmental and ecological standpoint, an RNA interference (RNAi) mediated double-stranded RNA (dsRNA)-based strategy can effectively manage forest fungal pathogens. The RNAi approach explicitly targets and suppresses gene expression through a conserved regulatory mechanism. Recently, it has evolved to be an effective tool in combating fungal diseases and promoting sustainable forest management approaches. RNAi bio-fungicides provide efficient and eco-friendly disease control alternatives using species-specific gene targeting, minimizing the off-target effects. With accessible data on fungal disease outbreaks, genomic resources, and effective delivery systems, RNAi-based biofungicides can be a promising tool for managing fungal pathogens in forests. However, concerns regarding the environmental fate of RNAi molecules and their potential impact on non-target organisms require an extensive investigation on a case-to-case basis. The current review critically evaluates the feasibility of RNAi bio-fungicides against forest pathogens by delving into the accessible delivery methods, environmental persistence, regulatory aspects, cost-effectiveness, community acceptance, and plausible future of RNAi-based forest protection products.

Plants, anchored throughout their life cycles, face a unique set of challenges from fluctuating environments and pathogenic assaults. Central to their adaptative mechanisms are transcription factors (TFs), particularly the AP2/ERF superfamily-one of the most extensive TF families unique to plants. This family plays instrumental roles in orchestrating diverse biological processes ranging from growth and development to secondary metabolism, and notably, responses to both biotic and abiotic stresses. Distinguished by the presence of the signature AP2 domain or its responsiveness to ethylene signals, the AP2/ERF superfamily has become a nexus of research focus, with increasing literature elucidating its multifaceted roles. This review provides a synoptic overview of the latest research advancements on the AP2/ERF family, spanning its taxonomy, structural nuances, prevalence in higher plants, transcriptional and post-transcriptional dynamics, and the intricate interplay in DNA-binding and target gene regulation. Special attention is accorded to the ethylene response factor B3 subgroup protein Pti5 and its role in stress response, with speculative insights into its functionalities and interaction matrix in tomatoes. The overarching goal is to pave the way for harnessing these TFs in the realms of plant genetic enhancement and novel germplasm development.