Critical Reviews in Biotechnology最新文献

Peptide-based medications hold immense potential in addressing a wide range of human disorders and discomforts. However, their widespread utilization encounters two major challenges: preservation and production efficiency. Cyclotides, a class of ribosomally synthesized and post-translationally modified peptides (RiPPs), exhibit unique characteristics, such as a cyclic backbone and cystine knot, enhancing their stability and contributing to a wide range of pharmacological properties exhibited by these compounds. Cyclotides are efficient in the biomedical (e.g., antitumor, antidiabetic, antimicrobial, antiviral) and agrochemical fields by exhibiting activity against pests and plant diseases. Furthermore, their structural attributes make them suitable as molecular scaffolds for grafting and drug delivery. Notably, the mutated variant of kalata B1 cyclotide ([T20K] kalata B1) has recently entered phase 1 of human clinical trials for multiple sclerosis, building upon the success observed in animal trials. To enable large-scale production of cyclotides, it is crucial to further explore their remarkable structural and bioactive properties. This necessitates extensive research focused on enhancing the efficiency of the processes required for their production. This study provides a comprehensive review of the biological synthesis methods of cyclotides, with particular emphasis on various expression systems, namely bacteria, plants, yeast, and cell-free systems. By investigating these expression systems, it becomes possible to design production systems that are adaptable, economically viable, and efficient for generating active and pure cyclotides at an industrial scale. The advantages of biological synthesis over chemical synthesis are thoroughly explored, highlighting the potential of these expression systems in meeting the demands of large-scale cyclotide production.

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.

Millets, often overlooked as food crops, have regained potential as promising stable food sources of bioactive compounds to regulate blood sugar levels in the diabetic populace. This comprehensive review delves into various millet varieties, processing methods, and extraction techniques aimed at isolating bioactive compounds. The review elucidates the inhibitory effects of millet-derived bioactive compounds on key enzymes involved in carbohydrate metabolism, such as α-amylase and α-glucosidase. It further explores the relationship between the antibacterial activity of phenols, flavonoids, and anthocyanins in millets and their role in amylase inhibition. In particular, phenols, flavonoids, and proteins found in millets play pivotal roles in inhibiting enzymes responsible for glucose digestion and absorption. However, processing methods can either enhance or reduce the bioactive compounds, thereby influencing enzyme inhibition capacity. Studies underscore the presence of phenolic compounds with notable inhibitory activity in: foxtail, finger, barnyard, and pearl millet varieties. Furthermore, extraction techniques, such as Soxhlet and ultrasonic-assisted extraction, emerge as efficient methods for isolating bioactive compounds, thus enhancing their therapeutic efficacy. This review highlights the challenges in preserving the inhibitory activity of millets during processing and optimizing processing methods to ensure better retention of bioactive compounds. It also emphasizes the utilization of millet as a natural dietary supplement or functional food to manage diabetes and promote overall well-being.

Cyanobacteria, the only oxygenic photoautotrophs among prokaryotes, are developing as both carbon building blocks and energetic self-supported chassis for the generation of various bioproducts. However, one of the challenges to optimize it as a more sustainable platform is how to release intracellular bioproducts for an easier downstream biorefinery process. To date, the major method used for cyanobacterial cell lysis is based on mechanical force, which is energy-intensive and economically unsustainable. Phage-mediated bacterial cell lysis is species-specific and highly efficient and can be conducted under mild conditions; therefore, it has been intensively studied as a bacterial cell lysis weapon. In contrast to heterotrophic bacteria, biological cell lysis studies in cyanobacteria are lagging behind. In this study, we reviewed cyanobacterial cell envelope features that could affect cell strength and elicited a thorough presentation of the necessary phage lysin components for efficient cell lysis. We then summarized all bioengineering manipulated pipelines for lysin component optimization and further revealed the challenges for each intent-oriented application in cyanobacterial cell lysis. In addition to applied biotechnology usage, the significance of phage-mediated cyanobacterial cell lysis could also advance sophisticated biochemical studies and promote biocontrol of toxic cyanobacteria blooms.

Resveratrol is an antioxidant abundant in plants like grapes and peanuts and has garnered significant attention for its potential therapeutic applications. This review explores its chemical attributes, stability, and solubility, influencing its diverse applications and bioavailability. Resveratrol's multifaceted therapeutic roles encompass: antioxidant, cardioprotective, anti-inflammatory, neuroprotective, anti-aging, and anticancer properties. While traditionally studied in preclinical settings, a surge in clinical trials underscores resveratrol's promise for human health. Over 250 recent clinical trials investigate its effects alone and in combination with other compounds. Commercially utilized in food, cosmetics, supplements, and pharmaceuticals, the resveratrol market is expanding, driven by microbial fermentation. Microbes offer advantages over plant extraction and chemical synthesis, providing cost-effective, pure, and sustainable production. Microbial biosynthesis can be attained from carbon sources, such as glucose or xylose, among others, which can be obtained from renewable resources or agro-industrial wastes. While Saccharomyces cerevisiae has been the most used host, non-conventional yeasts like Yarrowia lipolytica and bacteria like Escherichia coli have also demonstrated potential. Genetic modifications such as increasing acetyl-CoA/malonyl-CoA pools, boosting the shikimate pathway, or multi-copy expression of pathway genes, allied to the optimization of fermentation strategies have been promising in increasing titers. Microbial biosynthesis of resveratrol aligns with the shift toward sustainable and renewable bio-based compounds, exemplifying a circular bioeconomy. Concluding, microbial fermentation presents a promising avenue for efficient resveratrol production, driven by genetic engineering, pathway optimization, and fermentation strategies. These advances hold the key to unlocking the potential of resveratrol for diverse therapeutic applications, contributing to a greener and sustainable future.

Astaxanthin (AXT), a natural carotenoid, has strong antioxidant and anti-ageing effects and can reduce ultraviolet light-induced damage to cells and DNA, stimulate the immune system, and improve cardiovascular disease prognosis. Despite its wide applications in the: nutraceutical, cosmetic, aquaculture, and pharmaceutical industries, AXT industrial production and application are hindered by natural source scarcity, low production efficiency, and high requirements. This review compares the qualitative differences of AXT derived from different natural sources, evaluates the upstream procedures for AXT expression in different chassis organisms, and investigates synthetic biology- and cell factory-based strategies for the industrial production of natural AXT. Synthetic biology is a promising novel strategy for reprogramming plants or microorganisms to produce AXT. Additionally, genetic engineering using cell factories extends beyond terrestrial applications, as it may contribute to the long-term sustainability of human health during space exploration and migration endeavors. This review provides a theoretical basis for the efficient and accurate genetic engineering of AXT from the microalga Haematococcuspluvialis, providing a valuable reference for future research on the biomanufacturing of AXT and other biological metabolites.

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.

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.

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.

Compounds containing chiral C-N bonds play a vital role in the composition of biologically active natural products and small pharmaceutical molecules. Therefore, the development of efficient and convenient methods for synthesizing compounds containing chiral C-N bonds is a crucial area of research. Nicotinamide-dependent oxidoreductases (NDOs) emerge as promising biocatalysts for asymmetric synthesis of chiral C-N bonds due to their mild reaction conditions, exceptional stereoselectivity, high atom economy, and environmentally friendly nature. This review aims to present the structural characteristics and catalytic mechanisms of various NDOs, including imine reductases/ketimine reductases, reductive aminases, EneIRED, and amino acid dehydrogenases. Additionally, the review highlights protein engineering strategies employed to modify the stereoselectivity, substrate specificity, and cofactor preference of NDOs. Furthermore, the applications of NDOs in synthesizing essential medicinal chemicals, such as noncanonical amino acids and chiral amine compounds, are extensively examined. Finally, the review outlines future perspectives by addressing challenges and discussing the potential of utilizing NDOs to establish efficient biosynthesis platforms for C-N bond synthesis. In conclusion, NDOs provide an economical, efficient, and environmentally friendly toolbox for asymmetric synthesis of C-N bonds, thus contributing significantly to the field of pharmaceutical chemical development.