Critical Reviews in Biotechnology最新文献

With antibiotic resistance on the rise, there is an urgent need for new antibacterial drugs and products to treat or prevent infection. Many such products in current use, for example human and veterinary antibiotics and antimicrobial food preservatives, were discovered and developed from nature. Natural selection acts on all living organisms and the presence of bacterial competitors or pathogens in an environment can favor the evolution of antibacterial adaptations. In this review, we ask if vultures, blow flies and other carrion users might be a good starting point for antibacterial discovery based on the selection pressure they are under from bacterial disease. Dietary details are catalogued for over 600 of these species, bacterial pathogens associated with the diets are described, and an overview of the antibacterial defenses contributing to disease protection is given. Biotechnological applications for these defenses are then discussed, together with challenges facing developers and possible solutions. Examples include use of (a) the antimicrobial peptide (AMP) gene sarcotoxin IA to improve crop resistance to bacterial disease, (b) peptide antibiotics such as serrawettin W2 as antibacterial drug leads, (c) lectins for targeted drug delivery, (d) bioconversion-generated chitin as an antibacterial biomaterial, (e) bacteriocins as antibacterial food preservatives and (f) mutualistic microbiota bacteria as alternatives to antibiotics in animal feed. We show that carrion users encounter a diverse range of bacterial pathogens through their diets and interactions, have evolved many antibacterial defenses, and are a promising source of genes, molecules, and microbes for medical, agricultural, and food industry product development.

Microbes have been extensively utilized for their sustainable and scalable properties in synthesizing desired bio-products. However, insufficient knowledge about intracellular metabolism has impeded further microbial applications. The genome-scale metabolic models (GEMs) play a pivotal role in facilitating a global understanding of cellular metabolic mechanisms. These models enable rational modification by exploring metabolic pathways and predicting potential targets in microorganisms, enabling precise cell regulation without experimental costs. Nonetheless, simplified GEM only considers genome information and network stoichiometry while neglecting other important bio-information, such as enzyme functions, thermodynamic properties, and kinetic parameters. Consequently, uncertainties persist particularly when predicting microbial behaviors in complex and fluctuant systems. The advent of the omics era with its massive quantification of genes, proteins, and metabolites under various conditions has led to the flourishing of multi-constrained models and updated algorithms with improved predicting power and broadened dimension. Meanwhile, machine learning (ML) has demonstrated exceptional analytical and predictive capacities when applied to training sets of biological big data. Incorporating the discriminant strength of ML with GEM facilitates mechanistic modeling efficiency and improves predictive accuracy. This paper provides an overview of research innovations in the GEM, including multi-constrained modeling, analytical approaches, and the latest applications of ML, which may contribute comprehensive knowledge toward genetic refinement, strain development, and yield enhancement for a broad range of biomolecules.

Buckwheat (Fagopyrum spp.) is a typical pseudocereal, valued for its extensive nutraceutical potential as well as its centuries-old cultivation. Tartary buckwheat and common buckwheat have been used globally and become well-known nutritious foods due to their high quantities of: proteins, flavonoids, and minerals. Moreover, its increasing demand makes it critical to improve nutraceutical, traits and yield. In this review, bioactive compounds accumulated in buckwheat were comprehensively evaluated according to their chemical structure, properties, and physiological function. Biosynthetic pathways of flavonoids, phenolic acids, and fagopyrin were methodically summarized, with the regulation of flavonoid biosynthesis. Although there are classic synthesis pathways presented in the previous research, the metabolic flow of how these certain compounds are being synthesized in buckwheat still remains uncovered. The functional genes involved in the biosynthesis of flavonols, stress response, and plant development were identified based on multi-omics research. Furthermore, it delves into the applications of multi-omics in improving buckwheat's agronomic traits, including: yield, nutritional content, stress resilience, and bioactive compounds biosynthesis. While pangenomics combined with other omics to mine elite genes, the regulatory network and mechanism of specific agronomic traits and biosynthetic of bioactive components, and developing a more efficient genetic transformation system for genetic engineering require further investigation for the execution of breeding designs aimed at enhancing desirable traits in buckwheat. This critical review will provide a comprehensive understanding of multi-omics for nutraceutical enhancement and traits improvement in buckwheat.

The ornithine-urea cycle (OUC) in fungal cells has biotechnological importance and many physiological functions and is closely related to the acetyl glutamate cycle (AGC). Fumarate can be released from argininosuccinate under the catalysis of argininosuccinate lyase in OUC which is regulated by the Ca²⁺ signaling pathway and over 93.9 ± 0.8 g/L fumarate can be yielded by the engineered strain of Aureobasidium pullulans var. aubasidani in the presence of CaCO₃. Furthermore, 2.1 ± 0.02 mg of L-ornithine (L-Orn)/mg of the protein also can be synthesized via OUC by the engineered strains of Aureobasidum melanogenum. Fumarate can be transformed into many drugs and amino acids and L-Orn can be converted into siderophores (1.7 g/L), putrescine (33.4 g/L) and L-piperazic acid (L-Piz) (3.0 g/L), by different recombinant strains of A. melanogenum. All the fumarate, L-Orn, siderophore, putrescine and L-Piz have many applications. As the yeast-like fungi and the promising chassis, Aureobasidium spp, have many advantages over any other fungal strains. Further genetic manipulation and bioengineering will enhance the biosynthesis of fumarate and L-Orn and their derivates.

Biohydrogen (H₂) is an efficient form of renewable energy generated from various biological organisms. Specifically, primitive plants such as algae which are photosynthetic organisms can produce several commercial products, including biofuels due to their simple form, short life span, efficient photosynthetic capacity, and ability to grow in non-potable water sources. But these algae are often neglected and considered waste. Several studies have revealed the importance and role of algal species in generating biofuels, especially biohydrogen. Considerable research has been conducted in order to understand hydrogen production from algal sources. This review emphasizes the photolysis of water-based hydrogen production in algae apart from the metabolites fermentation process. The influence of physico-chemical factors, including oxygen scavengers, nanoparticles, and hydrogenases, was highlighted in this review to enhance H₂ production from algal species. Also, several algal species used for hydrogen production are summarized in detail. Overall, this review intends to summarize the developments in hydrogen production from algal species keeping in view of excellent prospects. This knowledge certainly would provide a good opportunity for the industrial production of hydrogen using algal species, which is one of the most concerned areas in the energy sector.

Even after the centenary celebration of insulin discovery, there prevail challenges concerning insulin aggregation, not only after repeated administration but also during industrial production, storage, transport, and delivery, significantly impacting protein quality, efficacy, and effectiveness. The aggregation reduces insulin bioavailability, increasing the risk of heightened immunogenicity, posing a threat to patient health, and creating a dent in the golden success story of insulin therapy. Insulin experiences various physicochemical and mechanical stresses due to modulations in pH, temperature, ionic strength, agitation, shear, and surface chemistry, during the upstream and downstream bioprocessing, resulting in insulin unfolding and subsequent fibrillation. This has fueled research in the pharmaceutical industry and academia to unveil the mechanistic insights of insulin aggregation in an attempt to devise rational strategies to regulate this unwanted phenomenon. The present review briefly describes the impacts of environmental factors of bioprocessing on the stability of insulin and correlates with various intermolecular interactions, particularly hydrophobic and electrostatic forces. The aggregation-prone regions of insulin are identified and interrelated with biophysical changes during stress conditions. The quest for novel additives, surface-active agents, and bioderived peptides in decelerating insulin aggregation, which results in overall structural stability, is described. We hope this review will help tackle the real-world challenges of insulin aggregation encountered during bioprocessing, ensuring safer, stable, and globally accessible insulin for efficient management of diabetes.

Yeast has been established as a versatile platform for expressing functional molecules, owing to its well-characterized biology and extensive genetic modification tools. Compared to prokaryotic systems, yeast possesses advanced cellular mechanisms that ensure accurate protein folding and post-translational modifications. These capabilities are particularly advantageous for the expression of human-derived functional proteins. However, designing yeast strains as an expression platform for proteins requires the integration of molecular and cellular functions. By delving into the complexities of yeast-based expression systems, this review aims to empower researchers with the knowledge to fully exploit yeast as a functional platform to produce a diverse range of proteins. This review includes an exploration of the host strains, gene cassette structures, as well as considerations for maximizing the efficiency of the expression system. Through this in-depth analysis, the review anticipates stimulating further innovation in the field of yeast biotechnology and protein engineering.

Ene-reductase (ER) has been widely applied for asymmetrical synthesis of chiral intermediates due to its substrate promiscuity, photoexcited reactivity, and excellent property with producing two chiral centers at a time. Natural ERs often exhibit the same stereoselectivity, and they need to be engineered for opposite configuration of chiral compounds. The hydrogenation process toward activated alkenes by ERs is composed of reductive half reaction and oxidative half reaction, which are dependent upon two cofactors NAD(P)H and flavin mononucleotide. The catalytic activity of ERs will be affected by the size of the substrate, the activating strength of the electron-withdrawing groups, redox potential of cofactors, and the loop flexibility around catalytic cavity. Currently, protein engineering to ERs has been successfully employed to enhance various catalytic properties, including photoexcited asymmetric synthesis. This review summarizes the approaches to reverse the stereoselectivity and enhance catalytic activity of ERs and new applications of the engineered ERs in photobiocatalytic asymmetric synthesis, besides the discussion with the existing molecular mechanisms of mutants regarding the improved catalytic performance.

Natural products have long served as critical raw materials in chemical and pharmaceutical manufacturing, primarily which can provide superior scaffolds or intermediates for drug discovery and development. Over the last century, natural products have contributed to more than a third of therapeutic drug production. However, traditional methods of producing drugs from natural products have become less efficient and more expensive over the past few decades. The combined utilization of genome mining and synthetic biology based on genome sequencing, bioinformatics tools, big data analytics, genetic engineering, metabolic engineering, and systems biology promises to counter this trend. Here, we reviewed recent (2020-2023) examples of genome mining and synthetic biology used to resolve challenges in the production of natural products, such as less variety, poor efficiency, and low yield. Additionally, the emerging efficient tools, design principles, and building strategies of synthetic biology and its application prospects in NPs synthesis have also been discussed.

The human living environment serves as a habitat for microorganisms and the presence of ubiquitous airborne microbes significantly impacts the natural material cycle. Through ongoing experimentation with beneficial microorganisms, humans have greatly benefited from airborne microbes. However, airborne pathogens endanger human health and have the potential to induce fatal diseases. Tracking airborne microbes is a critical prerequisite for a better understanding of bioaerosols, harnessing their potential advantages, and mitigating associated risks. Although technological breakthroughs have enabled significant advancements in accurately monitoring airborne pathogens, many puzzles about these microbes remain unanswered due to their high variability and environmental diffusibility. Consequently, advanced techniques and strategies for special identification, early warning, and efficient eradication of microbial contamination are continuously being sought. This review presents a comprehensive overview of the research status of airborne microbes, concentrating on the recent advances and challenges in sampling, detection, and inactivation. Particularly, the fundamental design principles for the collection and timely detection of airborne pathogens are described in detail, as well as critical factors for eliminating microbial contamination and enhancing indoor air quality. In addition, future research directions and perspectives for controlling airborne microbes are also suggested to promote the translation of basic research into real products.