Trends in biotechnology最新文献

Invasive pest Spodoptera frugiperda, known as the fall armyworm (FAW), evolves rapid resistance to chlorantraniliprole (CAP) via symbionts, reducing traditional control efficacy and causing economic losses. To address the formidable challenge of insecticide resistance, we introduce phage therapy into pest control, enabling precise targeting and efficient lysis of symbionts that mediate resistance. We employ zein to synchronously encapsulate phages and insecticides, constructing a nano-insecticide. This nano-insecticide ensures stability, exhibits robust performance by protecting phages against temperatures up to 60°C, and enhances their survival under UV irradiation by 83-fold. It intelligently responds to the pest gut enzymes for precise and controlled release, improving FAW control by 17% and overcoming resistance. Additionally, pesticide residue is reduced by 82.4%, with minimal impact on soil and maize microbial communities, preserving seedling growth. This modular, eco-friendly framework offers a sustainable solution for resistant pests, addressing the escalating challenge of resistant pests and paving the way for advancements in sustainable agriculture.

Rewiring the metabolic flux for efficient microbial conversion requires robust, scalable gene assembly. However, conventional gene assembly approaches are labor-intensive, highly experience-dependent, and require extensive expertise to ensure reproducibility and efficiency. Even with advanced automation platforms such as biofoundries, assembling gene arrays with multiple transcriptional units (TUs) remains challenging. In this study, we present Efficient Modular Gene Assembly (EffiModular), an integrated in vitro and in vivo gene assembly platform compatible with automated workflows. EffiModular enables the assembly of up to eight TUs with 80% efficiency in a single transformation. Integrated into a biofoundry workflow, it enabled the construction of 120 distinct yeast strains with varying levels of expression of the β-carotene biosynthesis genes within 3 days. Compared with conventional approaches, it significantly reduces procedural complexity, minimizes reliance on operator expertise, and accelerates workflow timelines. These features establish EffiModular as a next-generation gene assembly platform for scalable, reproducible gene assembly in biofoundry-based genetic engineering.

Biofouling-the adhesion of organisms and their byproducts to submerged surfaces-poses economic and environmental challenges, highlighting the need for sustainable antifouling solutions. This study reports a proof-of-concept investigation into the environmental compatibility and field validation of natural cyclic peptides portoamides A and B (Pam) as a bio-based antifouling alternative. Pam have demonstrated antifouling activity by inhibiting mussel larval settlement and disrupting biofilm formation. Herein, the antifouling performance of Pam-engineered coatings was evaluated through anti-settlement, anti-biofilm, as well as marine field tests. Lab-scale tests revealed that Pam-based coatings (0.7 wt%) effectively reduced biofilm thickness, surface coverage, and mussel larval settlement. Field trials showed that Pam-functionalized coating prototypes outperformed a commercial biocide in use (Econea®), delaying macrofouling community establishment and contributing to enhanced antifouling effectiveness. Overall, this work supports further development of antifouling engineered systems using Pam, representing a significant technological advance (from Technology Readiness Level 3 to 6) toward sustainable marine coating systems.

The rapid growth of biodiesel production generates large amounts of crude glycerol, a low-value byproduct with environmental and economic challenges. Here, we present an engineered yeast coculture system combining Saccharomyces cerevisiae and Yarrowia lipolytica to convert crude glycerol into isopropanol, a liquid organic hydrogen carrier. The system integrates metabolic engineering, cell surface display pairing, immobilization, and continuous cultivation in fibrous bed bioreactors. In S. cerevisiae, glycerol use was improved by transporter optimization, pathway redirection, and flux shift from ethanol to isopropanol. In Y. lipolytica, ethanol from S. cerevisiae was redirected to isopropanol by acetyl-CoA reinforcement, malonyl-CoA diversion, and NADPH availability. Optimized pairing and inoculation ratios enhanced stability and yield. The consortia achieved complete glycerol utilization and three reuse cycles over 180 h. With pure glycerol, 28.34 g/l isopropanol was produced, while crude glycerol reached 86.06% of this yield. This strategy offers a scalable, modular route to convert biodiesel byproducts into bioenergy carriers.

Mesenchymal stromal cells (MSCs) are multipotent, fibroblast-like cells known for their paracrine activity rather than long-term engraftment. Their secretome-the ensemble of soluble factors and extracellular vesicles released by these cells-is emerging as a designable, off-the-shelf biotherapeutic. Advances in scalable bioprocessing, closed downstream processing, and smart delivery enable good manufacturing practice-ready translation. This review outlines a product-focused road map linking cell sourcing, preconditioning, and bioreactor expansion with downstream processing steps. We highlight bottlenecks, including heterogeneity, stability, dose definition, and validated potency assays, and address regulatory implications for classification, comparability, and release. By reframing the MSC secretome as a manufactured product rather than a biological extract, we propose strategies to speed clinical readiness and establish it as a reproducible next-generation biotherapeutic.

Paclitaxel, a clinically potent anticancer drug derived from Taxus species, faces persistent challenges in sustainable supply. Synthetic biology presents substantial opportunities for its de novo production, particularly with recent breakthroughs in elucidating its intricate biosynthetic pathways. However, its heterologous biosynthesis is significantly constrained by key bottlenecks, including pathway complexity, poor P450 expression, and inefficient metabolic flux. In this study, we explore how synthetic biology facilitates pathway decoding and reconstruction and propose strategies involving nonclassical chassis such as plant-associated cyanobacteria and filamentous fungi to enhance P450 compatibility. We also present a pragmatic framework for the rational application of state-of-the-art tools, including cell-free systems, synthetic microbial consortia, hybrid chemoenzymatic synthesis, and machine learning, to sustainably produce paclitaxel and other natural products.

While chimeric antigen receptor (CAR) T-cell therapy has become a standard of care in various blood cancers, its full curative potential for other diseases has yet to be maximized. One key limiting factor is progressive T-cell exhaustion and differentiation over time, leading to the loss of the CAR-expressing cells. CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein) gene manipulation to enhance CAR T-cell therapy has revolutionized the field in recent years. In this review, we will examine the application of CRISPR/Cas aimed at improving CAR T-cell function and persistence to combat the issues of exhaustion and dysfunction, with a focus on metabolic reprogramming. Understanding current preclinical CRISPR/Cas strategies for modulating CAR T-cell metabolism is critical in advancing CAR-T therapies to clinical applications.

The limited availability of genetic regulatory parts, especially terminators from non-model microorganisms, hampers precise gene regulation and the construction of efficient microbial cell factories. To address this problem, we developed a novel strategy for predicting and quantifying strong terminators genome-widely by integrating RNA-seq datasets with an insulated dual-reporter system. We validated 48, and 41 strong terminators in Zymomonas mobilis and Escherichia coli, respectively. Our results demonstrated notable cross-species compatibility of these terminators between the two bacteria and revealed that the length of the upstream sequence affects termination efficiency in Z. mobilis. We further applied selected strong terminators to enhance 2,3-butanediol production in Z. mobilis. This work thus establishes a pipeline for genome-wide prediction, quantitative assessment, and cross-species evaluation of bacterial terminators. It provides a valuable resource for expanding prokaryotic terminator libraries and engineering efficient microbial cell factories with refined transcriptional control.

Biofilms, complex and structured microbial communities encased within extracellular polymeric substances, represent an emerging area of interest in bioprocesses for the production of value-added chemicals. The properties of biofilms offer potential benefits for productivity and cost efficiency, yet the implementation of pilot- and large-scale productive biofilm processes remains a challenge due to their structural, ecological, metabolic, and physicochemical complexities. This review analyzes the key bottlenecks that limit the application of biofilms in productive bioprocesses, including mass transfer dynamics, ecological interactions, and bioreactor inefficiencies. It also highlights case studies of biofilm-based production and outlines key design principles for next-generation bioreactors. By identifying existing knowledge gaps and technological barriers, we anticipate that this review will facilitate the application of biofilms in industrial bioprocesses.

Type 1 diabetes (T1D) is caused by the autoimmune destruction of insulin-producing cells (IPCs), resulting in disruptions to blood glucose regulation. Cell therapy is an established, FDA-approved treatment for T1D. Incorporating IPCs into vascularized devices provides a promising strategy to enhance therapeutic efficacy. Here, we discuss the challenges of device vascularization and its role in successful IPC transplantation. We explore state-of-the-art engineering strategies used for the efficient vascularization of IPC encapsulation devices, including material selection, design criteria, and fabrication methods for the production and assembly of vascularization device components. In addition, the current state of research and future clinical applications in this field are discussed.