最新刊期
- 摘要：Adoptive T cell (ACT) therapy has revolutionized cancer immunotherapy with its targeted and durable anti-tumor potency, yet its broad clinical success, particularly against solid tumors, is severely compromised by two critical barriers: T cell exhaustion driven by persistent high-level T cell receptor (TCR) stimulation, and tumor immune escape via low-affinity mutations in tumor antigens. Conventional ACT manufacturing has long been guided by the paradigm of maximizing TCR stimulation strength to boost T cell activation and expansion, but this strategy frequently accelerates terminal T cell differentiation and irreversible exhaustion, while failing to address antigen mutational escape, creating an urgent unmet need for optimized, clinically translatable manufacturing protocols. In this study, we systematically investigated how initial TCR stimulation strength during in vitro manufacturing shapes the phenotypic state and anti-tumor effector function of T cells, using the well-established murine OT-1 CD8+ T cell model and clinically relevant human primary T cells including the 1G4 TCR-T system for solid tumor A375 cell targeting, and attenuated TCR stimulation via three readily translatable approaches: titrating down cognate antigen peptide concentration, using low-affinity antigen variants, and reducing the dosage of CD3/CD28 antibody-coated stimulatory beads. Our results demonstrated that moderately attenuated initial stimulation supported robust T cell activation and expansion, while significantly downregulating the expression of exhaustion-associated inhibitory receptors including PD-1, LAG3 and TIGIT. Functionally, weakly stimulated T cells exhibited faster cytotoxic kinetics against tumor cells, higher TNF-α secretion, and most notably, superior and sustained control of tumors expressing low-affinity mutant antigens both in vitro across multiple effector-to-target ratios and in an in vivo immunocompromised mouse tumor model, with these core findings fully recapitulated in human primary T cells and the 1G4 TCR-T system where attenuated stimulation enhanced antigen-specific cytotoxicity and proliferative capacity. Collectively, this study reveals that fine-tuning and moderately reducing initial TCR stimulation strength during in vitro manufacturing could serve as a facile, cost-effective and potential universal strategy to generate high-potency T cells for ACT, which mitigates T cell exhaustion and effectively counteracts antigen mutational escape, providing a practical and translatable rationale to optimize ACT manufacturing protocols and improve clinical outcomes for patients with advanced malignancies.关键词：Adoptive T cell;Stimulation strength;Tumor immunity;T cell exhaustion;Antigen mutational escape17|2|0更新时间：2026-05-12
- 摘要：Under the accelerating wave of global technological revolution and industrial transformation, synthetic biology has emerged as a cutting-edge interdisciplinary field integrating life sciences, engineering, and information sciences. Its "creative destruction" potential is reshaping the landscape of life and health industries. Foods for Special Medical Purposes (FSMPs) are specially processed and formulated to meet the unique nutritional needs of individuals with restricted eating, digestive or absorption disorders, metabolic disturbances, or other specific disease conditions. Beyond serving as a critical vehicle for clinical nutrition support, proactive health intervention, and the silver economy, FSMPs represent a systemic solution to improve clinical outcomes, reduce healthcare costs, and enhance quality of life. This study takes synthetic biology-empowered FSMPs as a typical case to systematically explore the opportunities, challenges, and development pathways. Through literature review, case studies, and research interviews, the paper analyzes how synthetic biology can fundamentally reshape FSMP industry in terms of raw material production, formula design, manufacturing models, industrial logic, and business models. The findings show that synthetic biology, following the “Design-Build-Test-Learn (DBTL)” paradigm, has enabled efficient biosynthesis of human milk oligosaccharides (HMOs), functional proteins, novel lipids, vitamins, and other high-value ingredients via enzymatic conversion, whole-cell catalysis, and microbial fermentation. Despite these advances, the transition from laboratory feasibility to industrial-scale application faces three major gaps: engineering scale-up instability, market cost and acceptance barriers, and regulatory approval uncertainties. To systematically address these challenges, the study proposes a coordinated governance model integrating technology, regulation, market, and ecosystem. The study concludes that synthetic biology holds transformative potential to drive the FSMP industry toward a new phase of precision, accessibility, and sustainability. However, breakthroughs in single dimensions are insufficient; multi-stakeholder coordination is essential to move from “technologically feasible” to “industrially viable, clinically accessible, and market-trusted.” The findings provide strategic pathways for leveraging synthetic biology to support high-quality development of the FSMP industry under China's 15th Five-Year Plan and the Healthy China initiative.关键词：synthetic biology;Foods for Special Medical Purposes (FSMPs);biomanufacturing;Regulation;Industrial transformation30|1|0更新时间：2026-05-12
- 摘要：Extracellular DNA (eDNA), an important component of environmental genetic material, has received increasing attention in environmental microbiology because of its diverse roles in bacterial community organization, genetic information transfer, and microbial adaptation to complex habitats. Unlike intracellular genomic DNA, bacterial eDNA exists outside cells in free, particle-associated, or matrix-bound forms, and can participate directly in ecological and biogeochemical processes. This review systematically summarizes current advances in the release mechanisms, functional attributes, environmental implications, and potential applications of bacterial eDNA. First, the major pathways responsible for eDNA release are discussed, including cell lysis-dependent mechanisms, such as autolysis, phage-induced lysis, and stress-triggered cell disruption, as well as secretion-dependent mechanisms mediated by membrane vesicles, secretion systems, and active export processes. Particular attention is given to quorum sensing, which can finely regulate eDNA production in response to population density, nutrient conditions, and environmental stress, thereby linking individual cellular processes with collective bacterial behavior. Second, the multifunctional roles of eDNA in bacterial ecosystems are reviewed. As a structural component of extracellular polymeric substances, eDNA contributes to biofilm formation, mechanical stability, surface adhesion, and niche construction. As a reservoir and platform for genetic exchange within biofilms, eDNA facilitates natural transformation and horizontal gene transfer, enhancing bacterial adaptability and evolutionary potential. In addition, eDNA may act as an important mediator in extracellular electron transfer, influencing microbial energy metabolism and redox-related environmental processes. Third, this review summarizes recent progress in the use of eDNA in environmental genetic risk assessment, biodiversity and species monitoring, pollutant bioremediation, and biofilm contamination control. Special emphasis is placed on the persistence and dissemination of functional genetic elements carried by eDNA, particularly antibiotic resistance genes and virulence genes, as well as their possible contribution to pathogen colonization and ecological health risks. These findings highlight eDNA as a critical link connecting molecular mechanisms, microbial community behavior, and environmental consequences. Finally, key challenges are discussed, including the integration of multiple release mechanisms, the relationship between structural heterogeneity and ecological function, the fate and transformation of eDNA under realistic environmental conditions, and risk control during environmental applications. Future studies should combine multiscale mechanistic analysis, in situ characterization, ecological effect evaluation, and biosafety-oriented application strategies, thereby promoting the development of eDNA research from descriptive observation toward mechanistic understanding and rational environmental implementation.关键词：extracellular DNA;release mechanism;biofilm structure;quorum sensing regulation;horizontal gene transfer68|4|0更新时间：2026-05-09
- 摘要：Artificial intelligence (AI) is profoundly reshaping the research paradigm of synthetic biology, shifting the design of living systems from empirically driven approaches to model-driven ones. Traditional synthetic biology relies on mutagenesis screening and trial-and-error optimization, making it difficult to address multiscale, high-dimensional, and strongly coupled biological processes. With the explosive growth of omics data, the widespread adoption of automated experimental platforms, and the rapid development of deep learning technologies, AI provides a new pathway to uncover sequence–structure–function relationships, build predictive biological models, and enable large-scale design of living systems. AI-driven synthetic biology has established a systematic framework across four key levels: at the biomacromolecular level, protein language models and generative structural models make de novo design of enzymes, receptors, and self-assembling materials possible; at the genomic level, deep learning advances modeling of mutational mechanisms, large-fragment sequence generation, and inference of phylogenetic dynamics, laying the foundation for programmable genome construction; at the cellular level, the integration of AI with mechanistic models accelerates virtual cell development, enabling quantitatively predictive descriptions of cellular behavior; at the platform level, multi-agent systems and automated "design–build–test–learn" (DBTL) cycles support end-to-end automation of pathway planning, enzyme function prediction, and experimental scheduling. Overall, AI is moving synthetic biology from local optimization to system-level generation, and from empirical exploration to predictive design, providing a core driving force for the controllable reprogramming of living systems and innovation in biomanufacturing.关键词：artificial intelligence;synthetic biology;biomanufacturing362|28|0更新时间：2026-05-07
- 摘要：It remains elusive how transcription factors (TFs) efficiently search for and localize enhancers. Unraveling the dynamic mechanisms is not only fundamental to understanding gene regulation but also provides a critical theoretical framework for engineering cellular signal transduction pathways. Classical models, including free diffusion model and facilitated diffusion model, posit that TFs diffuse freely through the nucleoplasm, engage in non-specific DNA binding, and navigate the genome via sliding, hopping, or intersegmental transfer until encountering their cognate enhancers. While these theories are well-supported by experimental evidence in prokaryotes, they lack validation in eukaryotes and fail to recapitulate the physicochemical complexity of the eukaryotic nucleus, particularly densely packed chromatin environment. To address the inefficiency inherent to random diffusion, the guided exploration model has emerged, proposing that nuclear "signpost" elements, such as specific chromatin structures or protein assemblies, direct TF trafficking. However, research into the identity of these signposts and the underlying "navigation mechanisms" remains in its infancy, with fundamental questions far outnumbering definitive answers. In recent years, the discovery of transcriptional condensates and short tandem repeats (STRs) inspired new insights. TFs harboring intrinsically disordered regions (IDRs) can undergo liquid-liquid phase separation (LLPS) to form biomolecular condensates. These condensates functionally mimic nuclear signposts, serving as spatial beacons that guide TF search processes and, as supported by emerging evidence, potentiate gene transcriptional activation. Concurrently, STRs are enriched surrounding enhancers, where they directly interact with TFs and play pivotal roles in eukaryotic gene regulation. Here, we review the canonical TF search models, the LLPS-driven formation of transcriptional condensates, and the functional roles of STRs in enhancer biology. We propose an integrated model wherein STRs and transcriptional condensates act in synergy to enable rapid and precise TF targeting within complex chromatin. This complementary mechanism, termed "guidance and enrichment, concentration and catalysis", resolves key inefficiencies of classical diffusion models and offers a conceptual framework for deciphering enhancer selection and engineering synthetic DNA regulatory sequences.关键词：Transcription factor;Enhancers;Guided exploration;Transcriptional condensates;Short tandem repeats72|23|0更新时间：2026-04-27
- 摘要：Photobiocatalysis is a synthetic strategy that integrates photocatalysis and biosynthesis, and has the capacity to drive numerous non-natural reactions. However, its large-scale application is constrained by issues such as high enzyme loading, expensive cofactors, and poor reaction stability. Recently, the research team led by Hui-Min Zhao at the University of Illinois Urbana-Champaign achieved a significant milestone in synthetic biology by successfully integrating photoenzymatic reactions into bacterial metabolic pathways. This pioneering advancement, reported in the scientific community, has established the first "E. coli production factory" capable of amplifying the production of unnatural products through the process of fermentation. This technology has been demonstrated to be capable of synthesising the phenol-indole compound 4-(2-(3a,7a-dihydro-1H-indol-3-yl)ethyl)phenol (DIEP) in its complete biosynthetic form. This research demonstrates not only the feasibility of achieving complete biosynthesis and engineered amplification of photoenzymatic reactions within living cells, but also validates the biological activity of the synthesized non-natural product, indicating the technology's industrial application potential. The present paper sets out the research findings and offers insights based on related studies, with a view to advancing photobiocatalysis from the proof-of-concept stage towards industrial production.关键词：synthetic biology;ene-reductases;photobiocatalysis;total biosynthesis;dual-phase fed-batch fermentation198|25|0更新时间：2026-04-08
- 摘要：C1 biotechnology is undergoing a paradigm shift - from "discovering nature" to "reconstructing nature" - and its strategic value is being fundamentally redefined. No longer a long-term option for biomanufacturing, it is now emerging as a critical pathway to reshape the fundamental logic of carbon-based industries and achieve carbon neutrality. China possesses the world's most abundant application scenarios and the most urgent industrial demands, yet its dependence on "root technologies" remains the greatest vulnerability. This article argues that China must move beyond the conventional mindset of "isolated breakthroughs" and instead pursue a systemic reconstruction of its innovation paradigm, industrial ecosystem, talent ecosystem, and standard-setting discourse. With strategic resolve, China can seize the historic opportunity of the global green industrial revolution and secure a leading position in the emerging carbon-based future.关键词：C1 biotechnology;paradigm shift;systemic reconstruction;carbon neutrality;industrial foundation159|38|0更新时间：2026-04-08
- 摘要：Novel food ingredients produced through advanced synthetic biology and precision fermentation technologies are rapidly reshaping the landscape of global food manufacturing. Compared with traditional agricultural sourcing or natural extraction, biomanufacturing offers a more sustainable, controllable, and scalable supply model that reduces dependence on seasonal variability, land resources, and environmentally intensive production chains. Continuous breakthroughs in metabolic engineering and microbial cell factories have substantially improved production yields, purity, and cost efficiency, enabling many bio-derived ingredients to transition from laboratory research to industrial application. However, the commercialization of these innovative ingredients is not determined solely by technological readiness. Instead, it is increasingly constrained by regulatory adaptability, approval efficiency, and public acceptance, particularly in jurisdictions where existing food safety frameworks were originally designed for conventional products rather than emerging production systems. This study employs L-ergothioneine, a naturally occurring antioxidant amino acid and a representative product of synthetic biomanufacturing, as a case to examine the regulatory and governance challenges facing novel food ingredients. Traditionally extracted from limited biological sources such as edible fungi, ergothioneine is now more efficiently produced via microbial fermentation, which provides higher purity, stable supply, and lower environmental impact. Despite international regulatory recognition and commercialization progress in regions such as the United States and the European Union, its market entry in China remains relatively slow. Through a comparative review of international approval pathways, including the U.S. GRAS system and the EU Novel Food framework, alongside China's pre-market authorization regime, this study identifies key structural barriers affecting domestic commercialization. These include ambiguous technical requirements, limited risk-tiered evaluation mechanisms, lengthy review timelines, and gaps between scientific evidence and consumer perception. Building on these findings, the paper proposes an adaptive regulatory framework that integrates four complementary dimensions: clarification of technical guidelines, risk-proportionate assessment, optimization of substantial equivalence mechanisms, and strengthened science-based risk communication. Rather than advocating for accelerated approval alone, this framework emphasizes improving regulatory predictability, transparency, and trust while maintaining high safety standards. By embedding process-based risk evaluation and dynamic post-market monitoring into the authorization pathway, regulators can better balance innovation promotion with precautionary governance. This research contributes both empirically and conceptually. Empirically, it provides a systematic analysis of the institutional constraints affecting the industrialization of biosynthesized ergothioneine in China. Conceptually, it advances a broader understanding of how food safety governance can evolve from static ingredient-based assessment toward adaptive oversight of novel production systems. The findings offer policy insights for accelerating the compliant market entry of domestically developed bio-manufactured novel food ingredients and for fostering a resilient regulatory environment that aligns technological innovation with public health protection.关键词：L-ergothioneine;synthetic biology;novel food ingredients;regulatory policy143|27|0更新时间：2026-04-07
- 摘要：Synthetic biology, as a cutting-edge technological field of the 21st century, is driving transformative changes across various industries such as pharmaceuticals, agriculture, and manufacturing. Synthetic biology manufacturing utilizes renewable resources as raw materials to produce a wide range of products through biological processes, characterized by its cleanliness, efficiency, and sustainability. It has become a strategic focus of competition among major global economies. Intellectual property protection serves as a critical mechanism for incentivizing innovation and ensuring the healthy development of industries. However, the existing system reveals certain delays and ambiguities when confronted with the disruptive nature of synthetic biology manufacturing technologies.This paper systematically analyzes the current state of global intellectual property protection for synthetic biology manufacturing, highlighting a protection model primarily based on patents and trade secrets, supplemented by various forms such as copyright, data intellectual property, and new plant variety rights. It also compares the differences and trends in policies and judicial practices among the United States, the European Union, Japan, South Korea, and China. The study further identifies core challenges in intellectual property protection in this field, including the underutilization of intellectual property as a bridge between innovation and industry, insufficient application of patent data in R&D and AI training, limited applicability of standard essential patents and patent pools, lack of integration between regulatory approval systems and intellectual property protection, intellectual property dilemmas in pilot-scale platforms, and difficulties in evidence collection and infringement determination during enforcement.To address these issues, this paper proposes a series of systematic strategies to improve China's intellectual property protection system for synthetic biology manufacturing across five dimensions: top-level design, judicial protection, administrative systems, technological support, and industrial ecosystem. These strategies include formulating national strategies, refining judicial guidelines, establishing approval linkage mechanisms, promoting data empowerment and technological standardization, and fostering a collaborative intellectual property ecosystem. The aim is to build an intellectual property governance system that aligns with the industry's development stage, possesses international competitiveness, and effectively incentivizes innovation.关键词：synthetic biology;Bio-manufacturing;intellectual property protection;Patent110|19|0更新时间：2026-03-18
- 摘要：Eukaryotic microalgae can efficiently synthesize organic compounds by directly utilizing carbon dioxide and light energy, while naturally possessing the ability to synthesize lipids, pigments, terpenes, and various secondary metabolites, which gives them unique advantages in the construction of synthetic biology cell factories. However, in practical production processes, microalgae still face challenges such as relatively slow growth rates, limited accumulation of target products, and high cultivation costs. These issues impose certain constraints on its large-scale production and industrial application. Metabolic engineering and synthetic biology techniques provide effective ways to enhance the performance of microalgae in response to this issue. Systematic modification of the central metabolic network and product synthesis pathways can optimize intracellular carbon flow allocation, improve photosynthetic efficiency, and enhance the ability to synthesize target products. These measures significantly broaden the range of products that microalgae can synthesize. This article discusses the important progress in the development of genetic elements such as promoters, terminators, and screening markers for model species such as Chlamydomonas reinhardtii, Nannochloropsis sp., and Phaeodactylum tricornutum, which have been extensively studied. The successful application of genome editing technologies such as CRISPR/Cas9 in microalgae has made gene knockout, knock in, and precise regulation possible. In addition, representative metabolic regulation strategies in the field of synthetic biology were reviewed, with a particular focus on the optimization and reconstruction of metabolic networks, the application of "push-pull-block" regulation strategies and subcellular organelles engineering, as well as the supplementation of cofactor levels, aiming to enhance the accumulation of high-value compounds in microalgae and/or adjust the relative composition of metabolites. Moreover, the application potential of the integration of artificial intelligence (AI) technology and multi-omics data in the screening of microalgal cultivation conditions and metabolic pathway optimization is discussed. We also discuss the potential application of artificial intelligence technology and multi-omics data in microalgae cultivation condition screening and metabolic pathway optimization, and presents the results of engineered modifications of microalgae cell factories for the synthesis of high-value compounds in practical applications. Finally, an outlook on the application prospects and development directions of microalgae chassis cells is provided, including the construction of "directed microalgae chassis", the application of artificial intelligence technology in microalgae chassis design, novel organelle targeting signals, and the integrated utilization of microalgae chassis, aiming to provide guidance for eukaryotic microalgae synthetic biology.关键词：microalgae;artificial intelligence;metabolic engineering;synthetic biology;high-value products100|36|0更新时间：2026-03-02
- 摘要：As a key chemical raw material, 1,4-Butanediol (1,4-BDO) is widely utilized in various industries, including pharmaceuticals, materials science, textiles, and the defense industry sector. With increasingly stringent environmental protection policies worldwide, the shortcomings of conventional 1,4-BDO synthesis, such as the use of costly catalysts and high energy consumption, have become more pronounced. An abundance of renewable lignocellulosic biomass has great potential in the production of clean fuels and chemicals. The preparation of fermentable sugars from renewable lignocellulosic biomass is the key step in biorefinery. Based on synthetic biology approaches, the development of a low-carbon, cost-effective, and sustainable biosynthetic route for 1,4-BDO synthesis gains great interest. However, the coexistence of multiple fermentable sugars in lignocellulosic hydrolysates reduces carbon source utilization efficiency. After several physical and chemical pretreatment methods proceeded, the fermentation inhibitors generated during the pretreatment process can impair microbial metabolic activity as well, thereby lowering fermentation efficiency. Therefore, by using Escherichia coli as the microbial chassis, this review outlines strategies for constructing 1,4-BDO biosynthesis pathways in E. coli using different fermentable sugars as carbon sources. This review also summarizes genetic engineering approaches to enhance E. coli tolerance to fermentation inhibitors, including furfural, 5-hydroxymethylfurfural, organic acids, and phenolic substrates. We discuss the possibility of efficient co-utilization of mixed sugars, in situ detoxification, and higher-yielding 1,4-BDO production via the development of a multifunctional and modular microbial consortium with the help of division of labor and mutualism. Furthermore, by employing computational tools to mine and rationally design 1,4-BDO synthesis pathways, conducting simulations and optimizations based on genome-scale metabolic network models, and applying intelligent design to key enzymes involved in 1,4-BDO biosynthesis, it is expected that 1,4-BDO synthesis efficiency can be further improved in the future. Overall, this review provides valuable insights and prospects for the construction of robust, high-yield E. coli-based microbial consortia for 1,4-BDO production.关键词：Escherichia coli;synthetic biology;Lignocellulosic hydrolysate;1,4-Butanediol167|27|0更新时间：2026-02-11
- 摘要：Future industries denote emerging sectors propelled by technological innovation, which are characterized by substantial growth potential and strategic significance, and play a crucial role in facilitating high - quality economic and social development. As a vital constituent of future industries, synthetic biology is distinguished by its highly interdisciplinary characteristics. It utilizes the Design-Build-Test-Learn (DBTL) cycle to surmount traditional technological bottlenecks and foster innovation. Simultaneously, the substantial uncertainty intrinsic to synthetic biology research and development (R&D) presents significant challenges for firms in ascertaining the timing, scale, and strategy of investment. Based on the resource - based view, technological innovation theory, and the IT productivity paradox, this study explores the influence of R&D investment strategies in synthetic biology on firms' operational performance. Using financial data and patent text information of 750 U.S. biotechnology firms from 2019 to 2021, this study utilizes the Latent Dirichlet Allocation (LDA) topic-modeling approach and cosine similarity to quantify R&D inputs. Subsequently, regression analysis is applied to investigate the influence of synthetic biology R&D investment on firms' operational performance, as well as the moderating effects of asset scale and liquidity. The findings indicate that: (1) There exists a significant inverted U-shaped relationship between the R&D investment in synthetic biology and firm performance; (2) Asset size and liquidity exert a positive moderating effect on this relationship; and (3) Once the firm scale surpasses a specific threshold, the inverted U-shaped relationship transforms into a U-shaped relationship. Based on these findings, three strategic perspectives are put forward: making early and small-scale investments to diversify risks and enhance marginal returns; making intelligent investments to optimize resource allocation during the growth of firms; and for large-scale firms, appropriately increasing R & D input to realize a positive transformation of the investment-performance curve. This study is among the pioneering studies to quantitatively capture the mechanism by which R & D investment in synthetic biology affects firm performance. It identifies the optimal investment models, enriches the theoretical comprehension of the input-output relationship in synthetic biotechnology, and offers practical strategic guidance for biotechnology firms.关键词：R&D investment in emerging technologies;Synthetic biotechnology;Firms' operational performance;patent analysis;Topic modelling;Firm resources141|12|0更新时间：2026-01-07
- 摘要：Global climate change and the energy crisis are driving the urgent need for sustainable biomanufacturing technologies. With the proposal of the "Carbon Peaking and Carbon Neutrality" goal, the microbial conversion of C2 compounds (such as acetic acid and ethanol) into high-value-added chemicals has become a key research focus in biorefining. Syngas fermentation, a representative third-generation biorefinery strategy, transforms syngas (mainly composed of H₂, CO, and CO₂) into a variety of chemicals through chemo-catalytic and microbial processes. A major advantage of syngas is its wide range of accessible sources. Syngas suitable for microbial one-carbon gas fixation can be recovered from industry exhaust streams, including metallurgical processes and power plants, which contributes to significant cost reduction. Current research on syngas-derived C2 substrates primarily focuses on acetic acid and ethanol. Microbial cell factories that utilize C2 substrates integrate carbon capture technology with the biosynthetic capabilities of industrial microorganisms, representing a viable pathway toward carbon-neutral bioproduction at this stage. However, challenges remain in the microbial utilization of C2 compounds, including low metabolic efficiency and limited tolerance. Extensive research in Escherichia coli has deepened our understanding of acetic acid metabolism, covering aspects such as cell growth, substrate transport, metabolic regulation, stress responses, laboratory evolution mechanisms and acetylation modification effects. This review focuses on the microbial metabolic pathways and metabolic engineering strategies for acetic acid and ethanol, evaluating their potential to produce a wide range of bio-based chemicals through the integration of synthetic biology and systems biology approaches. Future research should focus on rebuilding the metabolic networks of strains through systematic metabolic engineering and adaptive laboratory evolution to optimize carbon flux distribution and energy efficiency. Besides, by combining enzyme engineering with dynamic regulatory strategies, rate-limiting steps will be optimized as well as the accumulation of toxic intermediates reduced, thereby systematically improving the conversion efficiency and economic feasibility of C2 substrates. In addition, further development of combining microbial transformation and chemical catalysis, integrating C1 gas fixation with efficient C2 conversion technologies, will further support the negative-carbon biomanufacturing systems and the achievement of "carbon neutrality" goals.关键词：acetic acid;ethanol;syngas-derived;metabolic engineering;high value-added chemicals;synthetic biology445|18|0更新时间：2025-12-30
- 摘要：As a cutting-edge modality in synthetic biology-driven therapeutics, engineered probiotic consortia hold immense promise for disease intervention and treatment. However, the design and assembly methodologies for these synthetic ecosystems remain poorly systematized and lack comprehensive critical review. In this review, we begin by systematically reviewing and critically evaluating the current applications and therapeutic potential of common single-strain probiotics in the prevention and treatment of various diseases. Then, we provide a systematic summary for three primary assembly strategies for engineering these consortia, i.e., the heuristic cocktail strategy, the physical contact-dependent assembly strategy, and the small molecule-mediated contact-independent assembly strategy. The heuristic cocktail approach synergizes functionally complementary bacterial strains to achieve enhanced therapeutic effects, though it faces challenges in achieving precise functional coordination and control. The physical contact-dependent assembly strategy employs techniques such as genetically encoded adhesins, DNA-programmed assembly, and biomaterial encapsulation to improve gut colonization and delivery efficiency, yet balancing colonization stability with safety remains a significant challenge. In contrast, the molecule-mediated contact-independent strategy utilizes quorum sensing and metabolic cross-feeding to achieve precise control of synthetic probiotic consortia, although the low efficiency in constructing cross-species metabolic networks presents a major bottleneck. We critically examine the mechanistic principles, representative applications, and current limitations of each strategy. Looking forward, the field is moving beyond the refinement of individual strategies toward their synergistic integration. Combining the rapid prototyping and functional complementarity of the cocktail approach with the precise spatial organization and enhanced colonization offered by physical contact-based strategies, and further empowering the consortium with the dynamic, programmable regulation afforded by molecular communication, holds the key to constructing truly robust, efficient, and intelligent therapeutic ecosystems. This integrated approach, supported by advances in artificial intelligence and genome-scale metabolic modeling, promises to accelerate the rational design of next-generation synthetic probiotics. This comprehensive overview aims to provide a foundational framework and technical reference for developing advanced, safe, and effective synthetic probiotic therapies.关键词：probiotics;synthetic microbial consortia;cocktail strategy;microbial interactions;microbial ecology260|22|0更新时间：2025-12-30
- 摘要：Gas vesicles (GVs) are a class of protein-based, rigid, hollow organelles commonly found in aquatic microorganisms. They are assembled from gene clusters encoding complete gas vesicle synthesis pathways within the genome. Notably, homologous gas vesicle gene clusters are also widely distributed in soil streptomycetes, though their physiological functions remain unclear. In this study, we cloned the gas vesicle gene cluster gvpOAFGJLSK (gvp3234, 3.4 kb) from Streptomyces sp. CB03234 and introduced it into the model streptomycete Streptomyces albus J1074 via conjugative transfer. Although transmission electron microscopy (TEM) observations did not detect typical gas vesicle structures in the recombinant strain, heterologous expression of gvp3234 was found to significantly promote early growth of the host strain and trigger extensive metabolic reprogramming. Untargeted metabolomics analysis revealed that the accumulation levels of 170 metabolites were significantly upregulated in the recombinant strain. By comparison with databases, we confirmed a substantial increase in the production of various known bioactive compounds, including 2-aminobenzoic acid and albaflavenone, and identified 22 previously uncharacterized metabolites that were activated. Furthermore, heterologous expression of gvp3234 in another streptomycete, Streptomyces venezuelae ISP5230, also led to significant changes in the metabolome and activation of silent metabolic pathways. The study further demonstrated that heterologous expression of gvp3234 effectively enhanced the synthesis efficiency of heterologous enzyme proteins. This study is the first to report that heterologous expression of the gas vesicle gene cluster gvp3234 exhibits a universal function in two species of streptomycetes, enhancing the production of known metabolites and activating silent metabolic pathways in the host. These findings provide a novel tool and theoretical foundation for the rational optimization of target products and the discovery of new bioactive molecules in streptomycete metabolic engineering.关键词：gas vesicles;biosynthetic gene clusters;heterologous expression;Streptomyces albus;metabolites324|18|0更新时间：2025-12-30
- 摘要：(Objective)To systematically study the global distribution characteristics of Enterobacteriaceae harboring carbapenem resistance gene (blaKPC) and polymyxin resistance gene (mcr) based on NCBI database, as well as the genetic background of these resistance genes, providing a reference for disease prevention and control.(Methods)Whole-genome data of bacteria harboring blaKPC and mcr genes were downloaded from the NCBI database. Different subtypes of blaKPC and mcr genes in the strains were analyzed and identified. By annotating bacterial plasmids and identifying replicon types, the presence of these resistance genes in specific plasmids was revealed. The upstream and downstream genetic structures of the blaKPC and mcr genes were also analyzed.(Results)The bacteria co-harboring blaKPC and mcr genes were primarily from the Enterobacteriaceae family, with the main distribution in the United States, the United Kingdom, and China. The diversity of bacterial genera harboring both blaKPC and mcr genes increased from 2012 to 2018. The dominant genotype combinations were blaKPC-2+mcr-9.1 and blaKPC-3+mcr-9.1. In this study, the genotype blaKPC-2+mcr-9.1+mcr-9.2 was found in various STs of Escherichia coli (58, 46.03%). Genetic environment analysis showed that blaKPC is mainly located on the pKPC-CAV1193 plasmid, with a significant identification of the tnpR-tnpA-ISkpn7-blaKPC-ISkpn6 (Tn4401b) transposon structure. mcr-9.1 is mainly located on the IncHI2 (2A) plasmid, with conserved upstream and downstream genetic structures, the core structure being rcnR-rcnA-pcoE-pcoS-IS903B-mcr-9.1-wbuC-IS26.(Conclusion)Strains co-harboring the blaKPC and mcr genes show significant geographic distribution differences. Special attention should be given to the potential for transmission of specific ST types of Escherichia coli (such as ST167 and ST10) and their changes in clinical environments. The resistance genes blaKPC and mcr are transmitted through specific plasmids, pKPC-CAV1193 and IncHI2 (2A), respectively, and spread via transposons and other mobile genetic elements, greatly increasing the risk of resistance transmission, which warrants urgent attention.关键词：blaKPC;mcr;Enterobacteriaceae;plasmid;transposon;MGEs8|4|0更新时间：2025-11-10
- 摘要：Driven by an intensifying global protein shortfall, the alternative-protein sector has entered a phase of rapid capacity expansion and iterative technological upgrading. China now leads in both absolute volume and annual growth of alternative-protein patent applications, yet remains under-represented in high-value patent families and overseas jurisdictions, constraining its international competitiveness. This paper first dissects the global protein crisis and the consequent rise of alternative proteins. It then provides a panoramic scan of worldwide and domestic industrial landscapes and competitive dynamics. Finally, by applying a big-data patent lens to three technology tracks—single-cell protein, cell-cultured meat and plant molecular agriculture—the study offers a systematic roadmap of technological innovation and patent landscape designed . Our focus is on analyzing global patent filing trends and mapping the development of specific fields to identify major players. The study includes a detailed breakdown of leading companies' patent portfolios, assessing their volume and key technological areas. Based on these analyses, several recommendations are proposed to accelerate the development of China's alternative protein industry, such as establishing a foundational patent system to breakthrough key platform technologies, strengthening global patentllandscape, and enhancing international competitiveness.While a global leader in patent volume, China's alternative protein sector must navigate a crucial strategic repositioning to evolve from a patent giant into an industrial leader. Future strategy should be built on three pillars: cultivating high-value patents with global protection, particularly for critical attributes like safety and efficacy, to ensure regulatory compliance and international market access; fostering an enterprise-driven innovation ecosystem that rapidly translates research and experimental development into market-ready solutions through full industry chain collaboration; and actively participating in global governance to transition from a technology adopter to a co-architect of international standards and regulations. Achieving this will solidify China's pivotal role in the global alternative protein landscape, directly contributing to national food security and low-carbon development goals.关键词：Alternative protein;Single-cell protein;Microbial protein;patent analysis;synthetic biology11|11|0更新时间：2025-11-06
- 摘要：High-throughput genome editing is an effective approach to rapidly analyzing the function of massive genetic mutations and to performing genetic breeding. Compared with random mutagenesis, the Clustered, Regularly Interspaced Short Palindromic Repeats (CRISPR)-based genome editing is more efficient and programmable. High-throughput genome editing and screening is enabled by the design of guide RNA libraries targeting specific genes. In recent years, the high-throughput genome editing toolbox is enriched by various CRISPR systems and CRISPR-derived technologies. Here we review major CRISPR-based high-throughput genome editing methods, including CRISPR-assisted homology directed repair, base editing systems, and prime editing systems, and discuss their applications in different fields, including industrial microbial strain breeding, functional human genomics research and crop improvement. These methods were applied in enhancing the tolerance and production capacity of microorganisms in industrial microbial strain breeding, analyzing the functions of disease-associated single nucleotide variants (SNVs) in functional human genomics research, and enhancing the herbicide resistance of plants in crop improvement. To conclude, we discuss the limitations of these methods, including the limited species applicability, the low mutation diversity, the narrow editing window, and the difficulty in multiplex genome editing. We provide prospects to address these limitations, including, firstly, expanding the applicable species from model organisms such as Escherichia coli, Saccharomyces cerevisiae to other important industrial microorganisms such as Actinomycetes and Pseudomonas aeruginosa by using related CRISPR systems; secondly, increasing mutation diversity by developing more advanced editors, particularly for base editors; thirdly, broadening the targeting region of genome editors by using PAM-relaxed or computationally designed Cas variants, as well as novel base editor and prime editor architectures; fourthly, scaling up multiplex genome editing for more targeted sites. With the development of artificial intelligence and automation platforms, as well as the continued rapid advancement of CRISPR and its derivative technologies, we expect that more advanced high-throughput genome editing technologies will emerge.关键词：CRISPR;genome editing;high-throughput;homology directed repair;base editing;prime editing13|13|0更新时间：2025-11-03
- 摘要：Microbial electrosynthesis (MES) stands as a cutting-edge and promising technology that harnesses the metabolic capabilities of microbial cells to drive the conversion of carbon dioxide (CO2) into a diverse range of value-added chemicals, with electrons derived from the cathode serving as the critical reducing power. This innovative approach not only offers a potential solution to mitigate anthropogenic CO2 emissions but also presents a sustainable route for the production of high-value compounds, bridging the gap between environmental remediation and industrial biotechnology. However, despite the significant progress made in recent years, several key limitations persist in the field of MES. A major hurdle lies in the incomplete mechanistic understanding of the underlying processes, particularly regarding the intricate interactions between the microbial cells and the electrode surfaces, as well as the precise regulatory mechanisms governing electron uptake and carbon fixation. Additionally, the efficient utilization of one-carbon conversion pathways from various substrates remains a challenge, with many pathways exhibiting suboptimal activity or being restricted to specific substrates, thereby limiting the versatility and applicability of MES systems. Given these constraints, a comprehensive analysis of different types of MES devices and their operational characteristics is of paramount importance. Each device configuration, whether single-chamber, dual-chamber, or more advanced designs, possesses unique features that influence mass transfer, electron transfer efficiency, and microbial growth conditions. By gaining a deep understanding of these device-specific properties, researchers can tailor and optimize one-carbon bioconversion pathways to match the requirements of different substrates, thereby maximizing the overall efficiency and productivity of the MES process. This customization of pathways based on device characteristics represents a crucial step towards unlocking the full potential of MES technology. Furthermore, the selection and implementation of nanomaterials in MES systems are closely intertwined with the design and basic principles of the MES devices. Nanomaterials, with their unique physicochemical properties such as high surface area, excellent conductivity, and tunable surface functionalities, have emerged as promising modifiers to enhance MES performance. However, the effectiveness of nanomaterials is highly dependent on the specific device architecture and operational parameters. For instance, in devices with limited mass transfer, nanomaterials that facilitate electron transfer at the electrode-microbe interface may be more beneficial, whereas in systems where microbial adhesion is a limiting factor, nanomaterials that promote biofilm formation could be prioritized. Thus, a thorough analysis of the interplay between MES devices, nanomaterials, and their strengthening mechanisms is essential to develop synergistic strategies for efficiency enhancement. In this context, we delve into the analysis of various MES device configurations, elucidating their core operational principles and highlighting their respective advantages and limitations. Concurrently, we evaluate the strengths and weaknesses of different biological one-carbon conversion pathways, considering factors such as energy requirements, carbon flux distribution, and product specificity. Moreover, we explore the multifaceted roles of nanomaterials in augmenting MES efficiency, with a particular focus on their ability to modulate extracellular electron transfer (EET) processes. Nanoparticles have been shown to exert significant effects on the expression of functional genes involved in EET, thereby enhancing the electron uptake capacity of microbial cells and promoting more efficient communication between the microbes and the electrodes. Despite the current challenges, including low Faradaic efficiencies, suboptimal substrate conversion rates, and limited product synthesis yields that relegate MES to the early stages of development, the technology holds immense promise as one of the most viable CO₂ conversion strategies for the future. Its inherent sustainability, coupled with the potential for integration with renewable energy sources to power the electrochemical reactions, positions MES as a key player in the transition towards a low-carbon economy. By addressing the existing limitations through interdisciplinary research that combines microbiology, electrochemistry, materials science, and metabolic engineering, MES has the potential to make a substantial contribution to advancing sustainable biotechnology strategies and realizing a more environmentally benign and resource-efficient future.关键词：microbial electrosynthesis;CO2 fixation;electron transfer;nanobiotechnology;biosynthesis5|7|0更新时间：2025-10-21
- 摘要：One-carbon (C1) compounds—including CO2, CO, methane, methanol, and formate—have emerged as strategic feedstocks for next-generation biomanufacturing owing to their abundance, economic viability, and renewability. However, the efficient biological conversion of C1 substrates into valuable products is hampered by several fundamental challenges,including the low intrinsic efficiency of natural carbon fixation pathways, the thermodynamic and kinetic barriers in engineering efficient de novo artificial assimilation routes, the cytotoxic effects of reactive intermediates like formaldehyde, and the generally suboptimal industrial robustness and slow growth of both native and synthetic C1-utilizing microbes. Recent breakthroughs in synthetic biology and metabolic engineering have substantially mitigated these constraints, thereby accelerating C1 bioconversion and establishing a novel paradigm for carbon-neutral, green biomanufacturing. This review systematically examines state-of-the-art strategies and technological milestones reported between 2022 and 2025, with a focus on (i) Metabolic rewiring of native C1-utilizing microorganisms to enhance both C1-assimilation efficiency and product-synthesis capacity, (ii) de novo design of non-natural C1 assimilation pathways to provide more efficient route for the construction of C1-utilizing cell factories, and (iii) engineering artificial C1-utilizing cell factories through reconstituting natural or artificial C1 assimilation modules in well-established industrial fermentation strains to establish platform strains for C1-based bioproduction. Moving beyond strategy description, we provide a comparative analysis of the metabolic characteristics, advantages, and limitations of key natural and synthetic C1 assimilation pathways. We further evaluate the applicability of various microbial hosts for the synthesis of target products ranging from biofuels and bulk chemicals to specialized metabolites. A critical discussion addresses the persistent technical bottlenecks, such as low activity of key C1 assimilation enzymes, poor biomanufacturing capabilities of natural C1-utilizing bacteria, and the challenges in achieving high flux through artificial pathways in vivo. Finally, we explore the synergistic potential of integrated solutions—combining adaptive laboratory evolution, enzyme engineering, computational modeling, and systems-level analysis—to boost C1 utilization. We conclude by highlighting the transformative role of interdisciplinary convergence and artificial intelligence in accelerating the design-build-test-learn cycle, thereby paving the way for a sustainable, C1-driven bioeconomy.关键词：one-carbon compounds;methylotrophy;synthetic biology;metabolic engineering;Green biomanufacturing15|16|0更新时间：2025-10-13
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