Biotechnology advances最新文献

Bioelectrochemical systems (BES) as environmental remediation biotechnologies have boomed in the last two decades. Although BESs combined technologies with electro-chemistry, -biology, and -physics, microorganisms and biofilms remain at their core. In this review, various functional microorganisms in BESs for CO₂ reduction, dehalogenation, nitrate, phosphate, and sulfate reduction, metal removal, and volatile organic compound oxidation are summarized and compared in detail. Moreover, interrelationship regulation approaches for functional microorganisms and methods for electroactive biofilm development, such as targeted electrode surface modification, chemical treatment, physical revealing, biological optimization, and genetic programming are pointed out. This review provides promising guidance and suggestions for the selection of microbial inoculants and provides an analysis of the role of individual microorganisms in mixed microbial communities and its metabolisms.

The global market demand for natural astaxanthin (AXT) is growing rapidly owing to its potential human health benefits and diverse industry applications, driven by its safety, unique structure, and special function. Currently, the alga Haematococcus pluvialis (alternative name H. lacustris) has been considered as one of the best large-scale producers of natural AXT. However, the industry's further development faces two main challenges: the limited cultivation areas due to light-dependent AXT accumulation and the low AXT yield coupled with high production costs resulting from complex, time-consuming upstream biomass culture and downstream AXT extraction processes. Therefore, it is urgently to develop novel strategies to improve the AXT production in H. pluvialis to meet industrial demands, which makes its commercialization cost-effective. Although several strategies related to screening excellent target strains, optimizing culture condition for high biomass yield, elucidating the AXT biosynthetic pathway, and exploiting effective inducers for high AXT content have been applied to enhance the AXT production in H. pluvialis, there are still some unsolved and easily ignored perspectives. In this review, firstly, we summarize the structure and function of natural AXT focus on those from the algal H. pluvialis. Secondly, the latest findings regarding the AXT biosynthetic pathway including spatiotemporal specificity, transport, esterification, and storage are updated. Thirdly, we systematically assess enhancement strategies on AXT yield. Fourthly, the regulation mechanisms of AXT accumulation under various stresses are discussed. Finally, the integrated and systematic solutions for improving AXT production are proposed. This review not only fills the existing gap about the AXT accumulation, but also points the way forward for AXT production in H. pluvialis.

Ralstonia eutropha H16, a facultative chemolithoautotrophic Gram-negative bacterium, demonstrates remarkable metabolic flexibility by utilizing either diverse organic substrates or CO₂ as the sole carbon source, with H₂ serving as the electron donor under aerobic conditions. The capacity of carbon and energy metabolism of R. eutropha H16 enabled development of synthetic biology technologies and strategies to engineer its metabolism for biosynthesis of value-added chemicals. This review firstly outlines the development of synthetic biology tools tailored for R. eutropha H16, including construction of expression vectors, regulatory elements, and transformation techniques. The availability of comprehensive omics data (i.e., transcriptomic, proteomic, and metabolomic) combined with the fully annotated genome sequence provides a robust genetic framework for advanced metabolic engineering. These advancements facilitate efficient reprogramming metabolic network of R. eutropha. The potential of R. eutropha as a versatile microbial platform for industrial biotechnology is further underscored by its ability to utilize a wide range of carbon sources for the production of value-added chemicals through both autotrophic and heterotrophic pathways. The integration of state-of-the-art genetic and genomic engineering tools and strategies with high cell-density fermentation processes enables engineered R. eutropha as promising microbial cell factories for optimizing carbon fluxes and expanding the portfolio of bio-based products.

Gene circuits, which are genetically engineered systems designed to regulate gene expression, are emerging as powerful tools in disease theranostics, especially in mammalian cells. This review explores the latest advances in the design and application of gene circuits for detecting and treating various diseases. Synthetic gene circuits, inspired by electronic systems, offer precise control over therapeutic gene activity, allowing for real-time, user-defined responses to pathological signals. Notable applications include synZiFTRs for T-cell-based cancer therapies, immunomagnetic circuits for combating antibiotic-resistant infections like MRSA, and caffeine-induced circuits for managing type-2 diabetes. Additionally, advanced designs such as TetR-Elk1 circuits for reversing insulin resistance, RNAi circuits for targeting cancer cells, and synthetic circuits for managing metabolic conditions like urate homeostasis and diet-induced obesity are highlighted. These gene circuits, tailored for mammalian cells, showcase immense potential in gene- and cell-based therapies for complex metabolic and immune-related disorders, paving the way for precise, customizable treatments. The review focuses on the use of these circuits in mammalian systems and emphasizes their therapeutic implications, offering insights into future developments in disease treatment.

In nature, various molecules possess spiral geometry. Such helical structures are even prevalent within the human body, represented classically by DNA and three-dimensional (secondary structure) protein folding. In this review, we chose helicenes and helicene-like structures -synthetically accessible carbon-rich molecules- as a compelling example of helically chiral scaffolds. Helicene chemistry, traditionally anchored in materials science, has been a subject of increasing interest in the biomedical field due to the unique optical and chiral properties of these helical structures. This review explores the diverse applications of helicenes in biomedicine, focusing on their role in cell imaging, protective coatings for implants, drug delivery systems, biosensors, and drug discovery. We discuss the unique properties of helicenes and helicene-like structures, highlighting their ability to form complex interactions with various biomolecules and their potential in the development of candidates for therapeutic agents. Recent advances in helicene derivatives with enhanced circularly polarized luminescence and other photochemical properties are also reviewed, underlining their utility in precise bio-imaging and diagnostic techniques. The review consolidates the current literature and emphasizes the growing importance of helicenes in bridging chemistry, materials science, and biology for innovative technological and biomedical applications.

Protein glycosylation, which involves the addition of carbohydrate chains to amino acid side chains, imparts essential properties to proteins, offering immense potential in synthetic biology applications. Despite its importance, natural glycosylation pathways present several limitations, highlighting the need for new tools to better understand glycan structures, recognition, metabolism, and biosynthesis, and to facilitate the production of biologically relevant glycoproteins. The field of bacterial glycoengineering has gained significant attention due to the ongoing discovery and study of bacterial glycosylation systems. By utilizing protein glycan coupling technology, a wide range of valuable glycoproteins for clinical and diagnostic purposes have been successfully engineered. This review outlines the recent advances in bacterial protein glycosylation from the perspective of synthetic biology and metabolic engineering, focusing on the development of new glycoprotein therapeutics and vaccines. We provide an overview of the production of high-value, customized glycoproteins using prokaryotic glycosylation platforms, with particular emphasis on four key elements: (i) glycosyltransferases, (ii) carrier proteins, (iii) glycosyl donors, and (iv) host bacteria. Optimization of these elements enables precise control over glycosylation patterns, thus enhancing the potential of the resulting products. Finally, we discuss the challenges and future prospects of leveraging synthetic biology technologies to develop microbial glyco-factories and cell-free systems for efficient glycoprotein production.

The depletion of fossil resources, coupled with global warming and adverse environmental impact of traditional petroleum-based plastics, have necessitated the discovery of renewable resources and innovative biodegradable materials. Lignocellulosic biomass (LB) emerges as a highly promising, sustainable and eco-friendly approach for accumulating polyhydroxyalkanoate (PHA), as it completely bypasses the problem of "competition for food". This sustainable and economically efficient feedstock has the potential to lower PHA production costs and facilitate its competitive commercialization, and support the principles of circular bioeconomy. LB predominantly comprises cellulose, hemicellulose, and lignin, which can be converted into high-quality substrates for PHA production by various means. Future efforts should focus on maximizing the value derived from LB. This review highlights the momentous and valuable research breakthroughs in recent years, showcasing the biosynthesis of PHA using low-cost LB as a potential feedstock. The metabolic mechanism and pathways of PHA synthesis by microbes, as well as the key enzymes involved, are summarized, offering insights into improving microbial production capacity and fermentation metabolic engineering. Life cycle assessment and techno-economic analysis for sustainable and economical PHA production are introduced. Technological hurdles such as LB pretreatment, and performance limitations are highlighted for their impact on enhancing the sustainable production and application of PHA. Meanwhile, the development direction of co-substrate fermentation of LB and with other carbon sources, integrated processes development, and co-production strategies were also proposed to reduce the cost of PHA and effectively valorize wastes.

Lignocellulosic biomass (LCB) is expected to play a critical role in achieving the goal of biomass-to-bioenergy conversion because of its wide distribution and low price. Biomass fermentation is a promising method for the sustainable generation of biohydrogen (bioH₂) from the renewable feedstock. Due to the inherent resistant structure of biomass, LCB needs to be pretreated to improve its digestibility and utilization. However, certain intermediates by-products generated during the pretreatment process, such as phenolic compounds, furan derivatives, and aldehydes, have been identified as potent inhibitors of subsequent anaerobic fermentation due to their disruptive effects on the physiological and metabolic functions of hydrogen-producing microbiota. To counteract the negative effects of these inhibitors on bio-H₂ fermentation, various detoxification strategies for LCB hydrolysates have been explored. This review presents a comprehensive analysis of fermentation-inhibitory by-products commonly generated by modern pretreatment protocols and their negative impacts on biohydrogen fermentation. Furthermore, the underlying mechanisms of inhibition upon hydrogen-producing microbes and their impacts on microbial community dynamics are exhibited. State-of-the-art strategies for detoxifying pretreated LCB have been also discussed, along with alternative pretreatment strategies designed to minimize or eliminate the formation of inhibitory by-products. Additionally, this review addresses the significant gap in the economic viability assessments of these processes, offering a detailed evaluation of both the technological and economic feasibility of biomass fermentation. Given the limitations of previous studies, strategies for cost-effective pretreatment and detoxification should be developed in the future to overcome the inhibition of fermentation inhibitors in the bioconversion of biomass to hydrogen.