Trends in biotechnology最新文献

Synthetic metabolism has the potential to transform carbon capture, bioremediation, or bioproduction strategies. To transfer metabolic designs from an in vitro context to living model systems such as the bacterium Escherichia coli, metabolic engineers incentivize the maintenance and use of the introduced metabolic module by making cell survival dependent on it (growth-coupled selection). However, creating and characterizing appropriately rewired selection strains is nontrivial and requires labor-intensive growth phenotyping in various conditions. To enhance the community use of extant selection strains, we compiled designs covering the central, amino acid, and energy metabolism of E. coli for this review, and we revisit the key concepts of growth-coupled selection.

Although stem cell technology has demonstrated considerable potential in correcting external auditory canal defects, conventional 2D differentiation techniques do not adequately replicate the in situ microenvironment, thereby hindering auricular chondrocyte differentiation. By contrast, 3D tissue-engineered scaffolds combined with bioprinting can delicately mimic the extracellular matrix (ECM), spatiotemporally releasing bioactive molecules in a controlled manner, thus enhancing stem cell differentiation. However, the mechanisms by which these scaffolds promote auricular chondrogenic differentiation remain largely unexplored. This review provides an overview of advancements in stem cell and tissue-engineered scaffolds for ear cartilage regeneration. By bridging the gap between cellular differentiation and material design, this review underscores how integrating bioengineering with developmental biology can facilitate auricular repair, offering novel strategies for the advancement of regenerative medicine.

Agricultural natural products (agri-NPs) from Streptomyces are a reservoir for green pesticide development, which is critical for global crop protection and food security. However, the discovery of novel agri-NPs with tailored bioactivity is challenging. In this forum article, we focus on specialized agri-NP discovery by harnessing interactions between Streptomyces and plants.

RNAi is a gene-silencing mechanism mediated by double-stranded RNA (dsRNA) molecules and is a promising pest control technology. However, challenges, such as limited persistence or narrow plant protection spectra in current RNAi application strategies, hinder its effectiveness against polyphagous pests. Here, we report an approach using plant probiotics to express dsRNA, propelling sustainable protection of multiple host plants. A Bacillus strain isolated from host plants of the polyphagous pest Hyphantria cunea, was engineered to express dsRNA targeting the pest. The modified SH-F8 strain significantly reduced H. cunea pupation rates and increased mortality by disrupting both energy metabolism and cuticle formation. The engineered SH-F8 strain exhibited successful colonization in two host plant species of H. cunea under field conditions, with enhanced population densities appearing under high-temperature/high-humidity conditions. This approach, termed 'Plant Probiotic-Based Gene Silencing' (PPGS), may offer a sustainable solution for multi-plant protection against polyphagous pests.

Biomaterial surface biofunctionalization refers to the process of modifying a biomaterial's surface to improve its interaction with biological systems. Controlling cell-material interactions is crucial, but current methods using native extracellular matrix (ECM) proteins, typically derived from human or animal tissue, or synthetic peptides are hampered by limitations such as batch variability, high cost, poor surface adsorption, and limited control over peptide presentation. This study introduces a technology that uses virus-like particles (VLPs) displaying biomimetic ECM-derived peptides. We engineered VLPs to present the RGD motif (arginine-glycine-aspartic acid), a well-established sequence that promotes cell adhesion, using either direct genetic fusion or SpyTag/SpyCatcher ligation, with the latter providing a more versatile conjugation strategy. These VLPs effectively functionalized cell-repellent silicone surfaces, significantly enhancing cell adhesion, migration, proliferation, and differentiation, achieving performance comparable with or exceeding that of native ECM proteins or synthetic RGD peptides. Additionally, the VLP/SpyCatcher particle enabled the co-presentation of multiple bioactive peptides, opening avenues for complex tissue engineering strategies. This tunable system represents a powerful tool for directing cell behavior, with significant potential for advancing nanomedicine and biomaterials development.

Organoid systems hold promise as miniaturized in vitro platforms that model developmental and pathological processes. However, the engineering of human bone marrow organoids (BMOs) has been a long-standing challenge. Recently, the field has witnessed the emergence of BMO-like systems, a potential paradigm shift for the study of human hematopoiesis and associated niche elements. Published protocols rely on the mesodermal induction of iPSCs, establishing mesenchymal-vascular-hematopoietic tissues exhibiting fetal compositional and functional features. However, concerns on their reliability to model adult bone marrow processes exist. Given the blood ontogeny complexity, leveraging developmentally inspired programs presents a significant challenge in establishing relevant BMO systems. While the importance of developing human BMO persists, the engineering modalities to achieve it remain cryptic.

Conjugated fatty acids (CFAs) are important for human health. They are traditionally obtained by extraction or chemical synthesis, but can alternatively be produced using biotechnology. Current efforts are aimed at improving the biotransformation process and capability for de novo biosynthesis. The next step is to make the process even more competitive.

Fungal biotechnology plays a vital role in advancing sustainability by offering innovative solutions for resource efficiency, environmental protection, and health improvements. Fungal systems are highly adaptable compared with other biotechnologies, with unique genomic and metabolic functions that enable the large-scale production of valuable compounds. This review emphasizes how fungal biotechnology contributes to global sustainability goals, particularly through artificial intelligence (AI)-driven methods that accelerate strain optimization and metabolic engineering. Engineered Aspergillus strains, with enhanced enzyme production, and Neurospora, a model organism, demonstrate significant potential for industrial applications. These advancements offer cost-effective and resource-efficient solutions, underscoring the importance of interdisciplinary collaboration in fungal biology, genomics, enzymes, and computational approaches to scale fungal biotechnology for sustainable outcomes.

Type 2 diabetes (T2D) is characterized by persistent and unresolved tissue inflammation caused by the infiltration and dysregulation of immune cells. Current therapeutics targeting inflammatory immune cells for T2D remain limited. In this study, we analyzed single cell RNA from metabolic organs in T2D, revealing increased macrophage accumulation and a pathogenic macrophage subpopulation defined as NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3)⁺ inflammatory and metabolically activated macrophages. To target these inflammatory cells, we developed nanovesicles encapsulating mitochondrial metabolic enzyme-related gene segments [immune-responsive gene 1 (IRG1)-overexpression plasmids] with cell membrane decoration. The nanovesicles functioned as cellular itaconate producers that elegantly circumvented the drug utilization barriers of a classic NLRP3 inhibitor and, as a mitochondria-reprograming system, mitigated fatty acid (FA)-associated metabolic dysfunction. The nanovesicles reversed inflammation, restored metabolic functions, and ameliorated obesity. Therefore, the metabolic and immunomodulatory functions of nanovesicles may offer translational opportunities for the prevention and treatment of T2D.

Acetogenic bacteria are attractive biocatalysts for biochemical production from sustainable single-carbon (C1) feedstocks. The major challenge is their energy-constrained anaerobic lifestyle, which results in slow growth and low productivity. To overcome this limitation, here, we investigate substrate cometabolism in the acetogen Eubacterium limosum, cofeeding either carbon monoxide or glucose as a dopant alongside the primary C1 substrate, methanol or formate. To increase experimental throughput, we developed AneVO, a parallel minibioreactor system that enables benchtop anaerobic batch and fed-batch cultivation, with continuous delivery of custom anaerobic gas blends. In all cofeeding scenarios, E. limosum grew faster, reached 52-254% higher cell densities, and exhibited 2.2- to 3-fold increase in acetate productivity. Most interestingly, cometabolism of CO and methanol synergistically improved growth and production. Together, these results validate AneVO as a low-cost resource for convenient benchtop cultivation of strict anaerobes and present a strategy for enhancing production from C1 feedstocks in an emerging model acetogen.