Current opinion in biotechnology最新文献

Tissue functions rely on complex structural, biochemical, and biomechanical cues that guide cellular behavior and organization. Synthetic cells, a promising new class of biomaterials, hold significant potential for mimicking these tissue properties using simplified, nonliving building blocks. Advanced synthetic cell models have already shown utility in biotechnology and immunology, including applications in cancer targeting and antigen presentation. Recent bottom-up approaches have also enabled synthetic cells to assemble into 3D structures with controlled intercellular interactions, creating tissue-like architectures. Despite these advancements, challenges remain in replicating multicellular behaviors and dynamic mechanical environments. Here, we review recent advancements in synthetic cell-based tissue formation and introduce a three-pillar framework to streamline the development of synthetic tissues. This approach, focusing on synthetic extracellular matrix integration, synthetic cell self-organization, and adaptive biomechanics, could enable scalable synthetic tissues engineering for regenerative medicine and drug development.

Biologically mediated adsorption and precipitation of phosphorus (P) from waste streams can restrict environmental P discharges. Here, we appraise progress in this field over the past decade. The research discipline has grown considerably in recent years. Industry 'wastes', including steel slags, continue to show promise as adsorbents with exceptionally high P retention capacities (>500 mg P g^-1). Hydrotalcite, a nanomineral, offers prospects as a P removal technology with imbedded climate change mitigation capacity. Biomineral struvite formation, driven by microbial processes, offers an exciting P removal and recovery approach that can be applied to diverse wastewater types due to its feedstock-independent mechanisms, emerging immobilisation techniques and adaptability to mixed cultures. All of these factors facilitate efficient nutrient recycling and scalable application to the wastewater industry. Adsorbed and precipitated P can be applied to cropland to offset dependence on conventional fertiliser inputs. Therefore, in addition to water treatment, these biologically mediated processes also offer opportunities to support food production. Moreover, as many of the input materials covered in this review are industry byproducts and common organic materials, the removal of P from waste streams by adsorption and precipitation offers strong circularity potential that aligns with the UN's Sustainable Development Goals. We call for future work to focus on long-term full-scale trials involving community, government and industry partners.

Optogenetics, an innovative approach integrating photonics and genetic engineering, enables precise control over molecular and cellular processes, opening up exciting new opportunities for precision-guided medicine. In this review, we highlight recent advances in optogenetic tools and their applications across a range of medical conditions, including vision restoration in retinitis pigmentosa via light-activated ion channels, precise immune response modulation in cancer immunotherapy, and blood glucose management in diabetes through controllable drug release. Optogenetics also plays a critical role in bioelectronic medicine, enabling seamless communication between electronic systems and biological tissues to enhance therapeutic precision. Finally, we discuss the challenges and potential transition of optogenetics from experimental models to clinical therapies, emphasizing its immense potential to transform future medical treatments.

Zymomonas mobilis is an ethanologenic bacterium that has been used for over 1500 years to produce alcoholic beverages. Recently, this microbe has become a top candidate for biofuel production due to its efficient metabolism. Z. mobilis is being developed to utilize lignocellulosic biomass as a feedstock and synthesize a range of valuable chemicals and fuels. Genetic and metabolic engineering strategies are crucial to reach these goals. Recent advances include genome engineering, CRISPR editing, and CRISPRi knockdown of genes. Metabolic engineering has enabled redirection of carbon from the natural product ethanol to chemicals such as 2,3-butanediol and polyhydroxybutyrate. The approaches summarized here will streamline the development of Z. mobilis as an industrial chassis for sustainable liquid fuels and chemicals.

Nonmodel microbes with unique advantages are emerging as industrial platforms, driven by advances in genetic engineering and omics technologies. Notable examples include the versatile soil bacterium Pseudomonas putida KT2440, the halophilic Halomonas bluephagenesis TD01, and the ethanologenic Zymomonas mobilis ZM4. While all three primarily use the Entner-Doudoroff pathway for glucose metabolism, they differ in various metabolic pathways and product synthesis. This review summarizes and compares their central carbon metabolism, advancements in genome engineering tools, and progress in scaling industrial applications from lab scale, to pilot scale, to full-scale commercial production. Understanding their similarities and differences informs future research on optimizing industrial applications and may guide the development of new microbial hosts.

Biocomputation aims to create sophisticated biological systems capable of addressing important problems in (bio)medicine with a machine-like precision. At present, computational gene networks engineered by single- or multi-layered assembly of DNA-, RNA- and protein-level gene switches have allowed bacterial or mammalian cells to perform various regulation logics of interest, including Boolean calculation or neural network-like computing. This review highlights the molecular building blocks, design principles, and computational tasks demonstrated by current biocomputers, before briefly discussing possible fields where biological computers may ultimately outcompete their electronic counterparts and achieve cellular supremacy.

Growing the bioeconomy requires products and pathways that are cost-competitive. Technoeconomic analyses (TEAs) aim to predict the long-term economic viability and often use what are known as n^th plant cost and performance parameters. However, as TEA is more widely adopted to inform everything from early-stage research to company and investor decision-making, the n^th plant approach is inadequate and risks being misused to inform the early stages of scale-up. Some methods exist for conducting first-of-a-kind/pioneer plant cost analyses, but these receive less attention and have not been critically evaluated. This article explores TEA methods for early-stage scale-up, critically evaluates their applicability to biofuels and bioproducts, and recommends strategies for producing TEA results better suited to guiding prioritization and successful scale-up of bioprocesses.

Recent advances in protein engineering have revolutionized the design of bionanomolecular assemblies for functional therapeutic and biotechnological applications. This review highlights the progress in creating complex protein architectures, encompassing both finite and extended assemblies. AI tools, including AlphaFold, RFDiffusion, and ProteinMPNN, have significantly enhanced the scalability and success of de novo designs. Finite assemblies, like nanocages and coiled-coil-based structures, enable precise molecular encapsulation or functional protein domain presentation. Extended assemblies, including filaments and 2D/3D lattices, offer unparalleled structural versatility for applications such as vaccine development, responsive biomaterials, and engineered cellular scaffolds. The convergence of artificial intelligence-driven design and experimental validation promises strong acceleration of the development of tailored protein assemblies, offering new opportunities in synthetic biology, materials science, biotechnology, and biomedicine.

Metabolic modeling is essential for understanding the mechanistic bases of cellular metabolism in various organisms, from microbes to humans, and the design of fitter microbial strains. Metabolic networks focus on the overall fluxes through biochemical reactions that implicitly rely on several biochemical processes, such as active or diffusive uptake (or export) of nutrients (or metabolites), enzymatic turnover of metabolites, and metal-cofactor enzyme interactions. Despite independent progress in biomolecular simulations, they have yet to be integrated to inform metabolic models. We explore the evolution of computational metabolic modeling approaches, starting with flux balance analysis, dynamic, kinetic delineations of metabolic shifts in single organisms within cells and across tissues, and mutually informing, community-level modeling frameworks and provide a narrative to tie in biomolecular simulations and machine learning predictions to usher the new phase of structure-guided synthetic biology applications. These additions and prospective novel ones are likely to open hitherto untapped paradigms for optimizing/understanding metabolic pathways toward improving bioproduction of protein and small molecule products with downstream applications in health, environment, energy, and sustainability.

Cerebral organoids pioneered in replicating complex brain tissue architectures in vitro, offering a vast potential for human disease modeling. They enable the in vitro study of human physiological and pathophysiological mechanisms of various neurological diseases and disorders. The trajectory of technological advancements in brain organoid generation and engineering over the past decade indicates that the technology might, in the future, mature into indispensable solutions at the horizon of personalized and regenerative medicine. In this review, we highlight recent advances in the engineering of brain organoids as disease models and discuss some of the challenges and opportunities for future research in this rapidly evolving field.