最新刊期
卷 6 ， 期 6 ， 2025
合成生物学创新赛专辑
张先恩，易啸
Editorial
- 摘要：The rapid advancement of life sciences and information technology has not only propelled synthetic biology into a prominent interdisciplinary frontier but has also spurred the vigorous development of the synthetic biotechnology and biomanufacturing industry, making it a key engine driving the new wave of scientific and technological revolution and industrial transformation. In this context, synthetic biology competitions, serving as a critical nexus connecting education, research, and industrial translation, are increasingly playing a bridging and catalytic role. By integrating disciplinary education, innovative practice, and startup incubation, these competitions effectively promote deep integration and collaborative development among multiple stakeholders in academia, research, and industry. This review systematically reviews the evolution and current state of synthetic biology and its competition systems, with a focus on analyzing the synergistic mechanisms of competitions in talent cultivation, disciplinary development, technological innovation, and industrial application. Synthetic biology competitions not only provide a platform for interdisciplinary learning and practice for students but also facilitate the alignment of university research resources with industrial application needs, thereby promoting the translation of basic research into industrial applications. Using the participation practice of Hubei University as a case study, this paper further elucidates the specific effects of competitions in stimulating students’ innovative potential, promoting the restructuring of curriculum systems, and advancing the practical application of research outcomes, demonstrating their exemplary value in constructing regional innovation ecosystems. However, the development of synthetic biology competitions currently faces several challenges. On one hand, the pathway for translating scientific research achievements into industrialization remains obstructed, with issues such as insufficient technological maturity and gaps in funding support. On the other hand, interdisciplinary collaboration still encounters institutional barriers, and deeper integration among fields such as life sciences, engineering, and computer science needs to be strengthened. Additionally, the competition systems themselves face issues including imperfect evaluation mechanisms, homogenization in track design, and a lack of biosafety and ethics education, which hinder their sustainable development. In response to the aforementioned challenges, this review proposes a series of actionable optimization strategies from five aspects: resource integration, optimization of evaluation mechanisms, diversified development of competition tracks, enhancement of biosafety education and ethical norms, and avoidance of competition homogenization. Specific measures include establishing an integrated resource platform for industry-university-research, improving an evaluation system oriented towards innovation and application potential, expanding differentiated tracks catering to various stages and needs; strengthening the integration of biosafety and ethics education, and promoting the alignment of competitions with regional industrial characteristics. In summary, as an important vehicle for promoting the integration of industry and education, the healthy development of synthetic biology competitions is of great significance for advancing technological innovation and industrial upgrading in the field of synthetic biology.Through systematic analysis and case discussions, this review undertakes to furnish valuable theoretical references and practical strategies for educational practices and policy formulation in related fields, thereby fostering the construction and refinement of synthetic biology innovation ecosystem.关键词：synthetic biology;synthetic biology competitions;industry-university-research;talent cultivation;bioeconomy137|18|0更新时间：2026-01-15
- 摘要：The continuous advancement of synthetic biology technology has significantly facilitated the transformation of probiotics, thereby enhancing the potential research of live biotherapeutic products (LBP) in therapeutic agents .In recent years, the use of LBP has been extensively applied as a promising approach for treating a wide array of diseases, including metabolic diseases. The standardization of procedures in the development of live biotherapeutic products—such as the careful selection of suitable chassis cells, the execution of precise engineering transformations, and the design of specialized genetic circuits tailored for specific diseases—has become a general process of this emerging field. Although clinical trials involving LBP for the treatment of metabolic diseases have not always yielded the anticipated results, they are gradually progressing toward clinical application. This article provides a comprehensive review of the latest advancements in live biotherapeutic products within the context of metabolic disease treatment, detailing the significant research progress made in addressing conditions such as phenylketonuria, hyperuricemia, and enteric hyperoxaluria, where LBPs are being explored as innovative therapeutic options. Furthermore, the article discusses the strategic development of LBP based on synthetic biology technology, highlighting the potential of these technologies to create sophisticated and targeted therapies capable of addressing complex metabolic pathways. However, it also acknowledges the challenges that lie ahead for live biotherapeutic products, including concerns related to safety, efficacy, and individual variability. These factors are crucial for the successful translation of live biotherapeutic products from the laboratory to the clinic. Confronting these hurdles, the article delineates ongoing endeavors to guarantee the safety and efficacy of live biotherapeutic products, alongside the advancement of personalized treatments tailored to each patient’s distinct genetic and metabolic profile.. Finally, the article presents a forward-looking perspective on the future development of live biotherapeutic products, anticipating the breakthroughs and advancements that will shape the next generation of metabolic disease treatments and the potential impact these biotherapeutics could have on improving patient outcomes and quality of life.关键词：live biotherapeutic products;metabolic diseases;synthetic biology;Microorganism;probiotics59|16|0更新时间：2026-01-15
- 摘要：Immunotherapy has transformed modern medicine by powerfully mobilizing the body's immune system to combat malignancies, infectious diseases, and autoimmune disorders. Despite remarkable clinical successes, current immunotherapeutic approaches face substantial limitations, including inadequate target specificity, dysregulated immune activation, and severe systemic toxicities. These challenges stem from the inherent complexity of biological systems and the pleiotropic nature of immune responses. Synthetic biology emerges as a transformative paradigm to address these limitations through rational engineering of immune cells and circuits. This discipline applies engineering principles to biological systems, enabling the design of sophisticated genetic circuits that confer precise spatiotemporal control over immune functions. This review comprehensively examines current synthetic biology strategies in immunotherapy, highlighting their mechanistic basis, clinical applications, and future directions for advancing precision medicine. Key innovations include: (1) engineered receptor systems (e.g., Syn-Notch, RASSL) that implement Boolean logic operations for enhanced target discrimination; (2) synthetic signaling cascades (e.g., CHOMP, SPOC) that convert pathological signals into therapeutic outputs; and (3) feedback-regulated circuits that dynamically modulate immune effector functions. These technologies have been successfully implemented in chimeric antigen receptor (CAR)-based therapies, where they improve tumor specificity while mitigating cytokine release syndrome and other adverse effects. Notably, synthetic biology facilitates the development of “smart” immunotherapies capable of environmental sensing, decision-making, and self-regulation. For instance, conditionally activated CAR-T cells demonstrate improved safety profiles through drug-inducible control systems, while synthetic cytokine circuits enable precise immune modulation. Furthermore, the integration of computational modeling with high-throughput screening accelerates the optimization of these engineered systems. Looking forward, synthetic biology promises to bridge critical gaps in conventional immunotherapy by enabling: (1) personalized therapeutic regimens through patient-specific circuit design; (2) multi-input diagnostic capabilities for complex disease microenvironments; and (3) robust safety mechanisms to prevent off-target effects.As the field advances, the convergence of genome editing, biomaterials science, and artificial intelligence will unlock even greater therapeutic potential for engineered immune cells.关键词：immunotherapy;synthetic biology;genetic circuits;cancer immunotherapy;engineered receptors;dynamic regulation54|9|0更新时间：2026-01-15
- 摘要：Polyhydroxyalkanoates (PHAs) represent a versatile class of microbial polyesters with exceptional biocompatibility, tunable biodegradability, and a broad range of mechanical and chemical properties. These characteristics make PHA highly suitable for diverse biomedical applications, including tissue engineering scaffolds, targeted drug delivery systems, wound dressings, and implantable devices. Notably, PHA degradation products such as 3-hydroxybutyrate are endogenous metabolites, which minimizes immunogenic responses and enhances long-term biocompatibility compared to conventional synthetic polymers. Recent advances in synthetic biology have significantly improved PHA biosynthesis. Metabolic engineering strategies, including CRISPR/Cas9-mediated genome editing for redirecting carbon flux toward PHA accumulation, CRISPR interference for modulating competing pathways, and optimization of promoter and ribosome-binding site (RBS) libraries, have enabled precise control over monomer composition and polymer properties. Additionally, microbial morphological engineering such as FtsZ-targeted cell elongation has been used to increase intracellular PHA content to over 90% of cellular dry weight. These developments have facilitated the synthesis of tailored PHA variants, ranging from rigid poly(3-hydroxybutyrate) (PHB) to elastomeric poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). Medical-grade PHA has shown significant translational potential across multiple therapeutic domains. Injectable porous microspheres composed of poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) have been developed for minimally invasive bone regeneration. Electrospun P34HB scaffolds exhibit simultaneous antibacterial and pro-angiogenic activities, accelerating wound healing. PHA-based nanocarriers enable sustained drug release for Alzheimer's disease and systemic lupus erythematosus treatment. Furthermore, virus-mimetic PHA particles have been exploited as adjuvant systems to enhance antigen presentation in tuberculosis and COVID-19 vaccine platforms. Future perspectives highlight the convergence of synthetic biology, materials science, and clinical translation to fully realize PHA’s biomedical potential. Next-generation industrial biotechnology (NGIB), which uses halophilic microorganisms for continuous fermentation under open conditions combined with advanced downstream purification protocols, is expected to improve the scalability and accessibility of medical-grade PHA. Integration with emerging technologies such as 3D bioprinting and organoid culture systems will expand PHA’s utility in complex, patient-specific tissue engineering applications. Collectively, these advances establish PHA as a highly promising foundational biomaterial platform for next-generation regenerative medicine and targeted therapeutic strategies.关键词：Polyhydroxyalkanoate (PHA);synthetic biology;Biomedical materials;Tissue engineering;Biocompatibility;Degradability69|6|0更新时间：2026-01-15
- 摘要：With the rapid expansion of lithium-ion battery (LIB) production driven by the global energy transition, the disposal of end-of-life batteries has emerged as a critical challenge due to resource depletion and environmental hazards. Conventional pyrometallurgical and hydrometallurgical recycling methods, while dominant, face significant drawbacks such as high energy consumption (exceeding 1000 ℃ for pyrometallurgy), substantial carbon emissions (about 3.5 tons CO2/ton of batteries), and toxic wastewater generation (pH<2, 2～3 tons/ton of batteries), underscoring the urgent need for sustainable alternatives. Biological recovery technologies, leveraging microbial metabolic activities, have gained prominence as eco-friendly, low-cost solutions for reclaiming strategic metals like lithium, cobalt, nickel, and manganese. This review systematically examines four core biotechnological approaches—bioleaching, biosorption, bioaccumulation, and biomineralization—detailing their mechanisms, advancements, and industrial scalability. Bioleaching, facilitated by acidophilic bacteria (e.g., Acidithiobacillus ferrooxidans, A. thiooxidans) and fungi (e.g., Aspergillus niger), employs microbial metabolites such as organic acids (citric, gluconic) and Fe³⁺/H₂SO₄ to dissolve metal oxides from battery “black mass,” achieving recovery rates of 60%～80% for Li and 85%～90% for Co/Ni under optimized conditions (30～40 ℃, pH 1.5～3.0). Innovations in fungal strain engineering and co-culture systems (e.g., sulfur- and iron-oxidizing bacteria) have enhanced leaching kinetics and metal selectivity, while response surface methodology (RSM) has optimized parameters like pulp density (1∶5～1∶10) and aeration (1 L/min). Biosorption exploits functional groups (e.g., carboxyl, amino) on microbial cell walls to immobilize metal ions via electrostatic interactions, with engineered strains like Escherichia coli expressing metallothioneins demonstrating 7-fold higher Ni²⁺ uptake. Bioaccumulation, enabled by synthetic biology, focuses on intracellular metal transport systems, such as NikABCDE transporters, though challenges like metabolic burden and metal toxicity persist. Biomineralization harnesses microorganisms (e.g., sulfate-reducing bacteria) to precipitate dissolved metals as stable minerals (e.g., MnCO3, NiS), which can be directly converted into electrode materials. For instance, fungal-synthesized MnCO3-derived MycMnOx/C composites exhibit exceptional supercapacitor performance (>350 F/g) and LIB cycling stability (>90% capacity retention after 200 cycles). Despite these advances, bottlenecks remain, including prolonged leaching cycles, scalability limitations, and the need for genetic engineering to enhance microbial metal tolerance and acid production. Emerging strategies, such as CRISPR-Cas9-mediated pathway optimization, biomimetic ion channels (e.g., NH2-pillar[5]arene for Li+ selectivity), and hybrid biohydrometallurgical processes, promise to bridge these gaps. Coupled with policy incentives and declining operational costs (projected at $1000～2000/ton, 25%～40% lower than hydrometallurgy), bio-recovery technologies are poised to revolutionize the LIB recycling industry, aligning with circular economy principles and achieving near-zero carbon emissions (<0.5 tons CO2/ton of batteries). Future research should focus on the convergence of synthetic biology, materials science, and process engineering to achieve industrial-scale implementation, ultimately fostering a truly sustainable and resilient battery supply chain.关键词：Bioleaching;Biosorption;Bioaccumulation;biomineralization;Battery recovery54|3|0更新时间：2026-01-15
- 摘要：Phenolic acid compounds are a class of secondary metabolites that are widely distributed in the plant kingdom, where they play essential roles in plant growth, development, and defense mechanisms. These compounds are known for their diverse bioactivities, including antioxidants, anti-inflammatory, anticancer, and antimicrobial properties, making them valuable natural products with significant therapeutic potential. In recent years, as understanding of their biological functions has deepened through advanced analytical techniques and molecular biology studies, phenolic acid compounds have shown increasingly promising potential for the applications in the fields of food preservation, nutraceuticals, pharmaceuticals, and cosmetics, particularly as natural alternatives to synthetic additives. However, the traditional method of obtaining these compounds through plant extraction is often limited by factors such as extraction efficiency, purity, and scalability, which are influenced by seasonal variations, plant species differences, and extraction methods. Recently, biosynthesis has emerged as a novel and promising approach to produce phenolic acid compounds in a more sustainable and controllable manner, addressing many of the limitations associated with conventional extraction methods. This review summarizes the application of biosynthesis in phenolic acid compounds production, focusing on recent advances in microbial fermentation and plant cell culture technologies. By employing genetic engineering and metabolic engineering techniques, including gene knockout, overexpression, and pathway optimization strategies, it is possible to significantly enhance the yield and purity of these compounds in various biological systems. For example, the overexpression of key enzymes involved in the phenylpropanoid pathway, such as phenylalanine ammonia-lyase (PAL) and cinnamate-4-hydroxylase (C4H), can lead to increased production of phenolic acids in both microbial and plant hosts. However, there are still many unknowns regarding the biosynthetic mechanisms of phenolic acids that require further investigation, particularly the pathway regulation and metabolic flux control. The regulatory mechanisms of different biosynthetic pathways and their expression variations among various plant species remain to be fully elucidated through comprehensive omics studies and comparative genomics approaches. In addition to biosynthesis challenges, the bioavailability and stability of phenolic acid compounds remain critical challenges that need to be addressed for their practical applications in commercial products. Phenolic acids are often prone to be degradative under certain conditions such as high temperature, extreme pH, or prolonged storage, which can limit their effectiveness and shelf-life in final formulations. Therefore, future research should focus on exploring the biosynthetic pathways of phenolic acid compounds in greater details using systems biology approaches, optimizing extraction and purification techniques to improve efficiency and purity through innovative separation technologies, and developing efficient biosynthetic systems using synthetic biology tools and high-throughput screening methods. These efforts will be crucial in realizing the widespread application of phenolic acid compounds across multiple fields including medicine, agriculture, food industry, and personal care products, ultimately contributing to the development of sustainable bioprocesses and value-added natural products.关键词：phenolic acid compounds;plant extraction;biosynthesis;Shikimic acid pathway;phenylpropane pathway;metabolic engineering71|11|0更新时间：2026-01-15
- 摘要：The enabling capabilities of synthetic biology (SynBio) are advancing at a rapid pace, with its applications increasingly integrated into daily life and generating significant social and economic impacts. Globally, nations are intensifying policy initiatives and resource allocations to secure strategic advantages in SynBio, seeking to harness its potential for biotechnological innovation and bioeconomic development. However, the development and application of SynBio are accompanied by emerging biorisks that may pose threats to human health and ecological security. These biorisks can be broadly categorized into two types: first, subjective biorisk arising from the intentional misuse of technology, such as illegal germline gene editing, bioterrorism, and the development of biological weapons; and second, objective biorisk resulting from non-intentional factors, including technical errors, negligence, or the inherent uncertainty of the technology itself, such as pathogenic leaks, gene escape, and biological invasions. Striking a balance between fostering innovation and ensuring safety has become a critical challenge for policymakers. In China, both hard law and soft law mechanisms respond to SynBio-related biorisks through different pathways. However, hard law-based governance faces structural difficulties, including gaps or delays in existing legislation and the practical challenges of enacting timely amendments or developing specialized laws. These obstacles reflect a fundamental tension between the stability and conservatism of law and the rapid evolution of SynBio. In this context, soft law has emerged as a promising alternative. Its flexibility, inclusiveness, and non-binding nature make it particularly well-suited to the dynamic and complex nature of SynBio and its associated risk governance needs. This paper analyzes the nature of biorisks in SynBio, and the regulatory challenges posed by current hard law frameworks. It then proposes a soft law-based approach to address these gaps. Through a comparative analysis of extraterritorial practices—primarily those of the United States—in the soft law governance of biorisks in SynBio, this paper identifies three strategic pathways for advancing soft law governance in SynBio: (1) developing soft law instruments that align with existing legal and ethical principles; (2) fostering a collaborative governance model centered on scientist self-governance + government guidance for the R&D phase; and (3) promoting a co-governance structure of industry self- discipline + government oversight for the application phase. The overarching goal is to enable innovation in SynBio while effectively protecting the public interest.关键词：synthetic biology;biorisks;soft law governance;scientist self-governance;industry self- discipline33|3|0更新时间：2026-01-15
Invited Review
- 摘要：Chemotaxis constitutes a fundamental mechanism underlying bacterial behaviors such as microbiota colonization and cancer therapy, while also representing an actively studied area within quantitative and synthetic biology. The indole induced bidirectional chemotaxis in Escherichia coli is mainly mediated by two methylation chemoreceptors (MCPs) with antagonistic effects, Tsr and Tar respectively, which was investigated in this study by mathematical model and experimental verification. Based on signal transduction dynamics model and Markov random walk model, the bidirectional chemotaxis of E. coli was described and simulated at both individual and population levels. Meanwhile, one of the MCPs receptors Tar was knockdown by 0%, 40% and 70% respectively via CRISPRi, and the chemotaxis behaviors of knockdown strains with different Tar expression levels under indole induction were observed and analyzed by Transwell migration experiment and self-designed microfluidics platform. The regulation of bacterial chemotaxis behavior was achieved in this study by adjusting the ratio of two antagonistic chemotaxis receptors Tsr and Tar, and together with mathematical model and experimental observation, the influence of Tsr/Tar ratio on the chemotaxis behavior of E. coli at individual and population level was preliminarily revealed in our study. This will benefit the quantitative analysis and precise regulation of chemotaxis behavior, as well as the future applications of bacterial chemotaxis in various fields.关键词：Chemotaxis;Indole;Bidirectional chemotaxis;CRISPRi;Microfluidics;quantitative biology39|4|0更新时间：2026-01-15
- 摘要：Transcription factors, as genetic switches, are used in synthetic biology to construct complex regulatory networks through modular combinations. Transcription factors are classified by two groups, repressors and activators. Repressors bind DNA and repress the expression level of downstream genes without inducers but will dissociate from DNA in the presence of inducers. The regulation type of repressor is called ON system, whereas activators bind DNA only after induced. The regulation type of activator is called OFF system. The goals to optimize transcription factors include identifying new substrates, enhancing sensitivity, adjusting dynamic range, and modifying regulation types. However, current types of engineered genetic elements are limited. Consequently, establishing an efficient platform of directed evolution for developing genetic switches is important for the design of genetic circuits and the optimization of metabolic pathways. In this study, we integrated in vivo directed evolution system of TADR (Targeted Artificial DNA Replisome) with a dual positive-negative selection system based on galactose kinase (GalK) and green fluorescent protein (GFP) to develop an experimental platform for optimizing genetic switches. The effectiveness of this platform was validated through experiments with transcription factor TetR. We successfully converted TetR from a repressor to an activator. In addition, we also converted transcription factor AcuR from a repressor to an activator (AcuR-OFF) which has not been reported before. The response of AcuR-OFF mutants to inducer is opposite to that of the wild type, but with similar dynamic range. Compared with the commonly used error-prone PCR technique, TADR is more affordable for construction of mutants library with higher genetic diversity. The dual positive-negative selection system greatly reduces the rate of false positives, and is able to screen in extreme cases where abundance of the target mutants within the population is low. This experimental platform is expected to be a powerful tool for the development and optimization of genetic switches, thereby advancing the research in synthetic biology.关键词：in vivo directed evolution;positive-negative selection;genetic switches;transcription factors;Escherichia coli55|6|0更新时间：2026-01-15
- 摘要：Antifreeze proteins (AFPs), a functionally unique and diverse class of biomolecules, possess the ability to depress the freezing point of aqueous solutions non-colligatively and inhibit the damaging process of ice recrystallization. These critical activities stem from their surface-adsorption mechanism at the ice-water interface, preventing ice crystal growth and maturation. Consequently, the strategic development of novel AFP analogues exhibiting significantly enhanced activity and stability represents an area of substantial research interest and practical value. Herein, we introduce and implement an “EKylation” strategy designed to rationally engineer the AFP (RCSB ID:5B5H) derived from the freeze-tolerant fungus Typhula ishikariensis. This approach specifically leverages the charge-tunable properties inherent to zwitterionic peptides to modify protein surfaces. We chemically coupled the synthetic zwitterionic polypeptide (EK)20, comprising alternating glutamate (E, negatively charged) and lysine (K, positively charged) residues, to the N-terminal structural domain of the wild-type 5B5H, which yielded the recombinant conjugate, designated 5B5H-EK. Comprehensive biophysical characterization revealed that the 5B5H-EK conjugate exhibited markedly enhanced structural stability compared to its unmodified counterpart. Crucially, this conjugation strategy led to a significant functional improvement, with the modified protein demonstrating a thermal hysteresis (TH) activity of 27.8%, representing a substantial enhancement over the wild-type AFP. Further insight into the molecular basis of this activity boost was gained through molecular dynamics (MD) simulations. These simulations indicated that the core ice crystal binding surface architecture of 5B5H-EK was largely preserved. Therefore, the conjugated zwitterionic chain significantly augmented the protein’s inherent ability to inhibit ice crystal growth and bind tenaciously to the ice surface. Analysis of water dynamics near the modified protein surface suggested that the (EK)20 chain promotes the formation of an extensive, short-range ordered hydration shell, effectively structuring interfacial water molecules into an “ice-water-like” layer distinct from bulk water. This engineered interfacial hydration likely contributes synergistically to the enhanced TH performance by reinforcing the AFP’s anchoring to the quasi-liquid layer and facilitating greater surface coverage. In conclusion, this study proposes a novel and effective protein engineering strategy, utilizing zwitterionic peptide conjugation (“EKylation”), for generating highly efficient antifreeze proteins and informs the rational design of next-generation, environmentally adaptable antifreeze materials.关键词：EKylation;antifreeze proteins;zwitterionic peptides;thermal hysteresis activity;molecular dynamics modelling49|4|0更新时间：2026-01-15
Research Article
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