Critical Reviews in Biotechnology最新文献

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.

Developing proteins with increased chemical space by expanding the amino acids alphabet has been an emerging technique to compete for the obstacle encountered by their need in various applications. 3,4-Dihydroxyphenylalanine (L-DOPA) catecholic unnatural amino acid is abundantly present in mussels foot proteins through post-translational modification of tyrosine to give a strong adhesion toward wet rocks. L-DOPA forms: bidentate coordination, H-bonding, metal-ligand complexes, long-ranged electrostatic, and van der Waals interactions via a pair of donor hydroxyl groups. Incorporating catechol in proteins through genetic code expansion paved the way for developing: protein-based bio-sensor, implant coating, bio-conjugation, adhesive bio-materials, biocatalyst, metal interaction and nano-biotechnological applications. The increased chemical spaces boost the protein properties by offering a new chemically active interaction ability to the protein. Here, we review the technique employed to develop a genetically expanded organism with catechol to provide novel properties and functionalities; and we highlight the importance of L-DOPA incorporated proteins in biomedical and industrial fields.

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.

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.

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.