Progress in molecular biology and translational science最新文献_第2页

Non-canonical amino acid incorporation via genetic code reprogramming in a cell-free translation system. 在无细胞翻译系统中通过遗传密码重编程的非规范氨基酸整合。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2025-10-22 DOI: 10.1016/bs.pmbts.2025.09.004

Harinarayana Ankamareddy, Hemasundar Alavilli, Vini Madathil, Sahil Kanjilal, Sushma Chauhan, Sudheer Dv N Pamidimarri

引用次数: 0

Computational biology for cell-free systems. 无细胞系统的计算生物学。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2025-09-17 DOI: 10.1016/bs.pmbts.2025.08.007

Mansi Acharya, Indra Mani

{"title":"Computational biology for cell-free systems.","authors":"Mansi Acharya, Indra Mani","doi":"10.1016/bs.pmbts.2025.08.007","DOIUrl":"10.1016/bs.pmbts.2025.08.007","url":null,"abstract":"Cell-free systems (CFS) decouple gene expression and metabolic pathways from living cells, offering a rapid, modular platform for biosensing, pathway prototyping, and protein production. This review surveys mechanistic and data-driven computational approaches tailored to CFS design and optimization. We compare deterministic ordinary differential equation (ODE) and stochastic simulation frameworks for modeling transcription-translation dynamics, describe adaptations of genome-scale metabolic models (GEMs) and flux balance analysis (FBA) for extract-based systems, and evaluate machine-learning strategies that learn sequence-to-function mappings from high-throughput cell-free assays. We summarize key software and discuss applications in paper-based diagnostics, reconstructed metabolic pathways, and high-yield cell-free protein synthesis. Recent advances in CRISPR based regulation using pre expressed dCas9 or RNA processing enzymes enable construction of multi-layer genetic circuits in extracts. Finally, we identify current gaps limited standardization of kinetic assays, sparse public datasets, and few hybrids kinetic-constraint modeling studies and propose a roadmap for community resources and hybrid modeling efforts that combine mechanistic clarity with machine learning (ML)-driven speed.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"218 ","pages":"65-85"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell free systems for production of chemicals. 用于生产化学品的无电池系统。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2025-11-27 DOI: 10.1016/bs.pmbts.2025.10.003

Sandeep Kaur, Gholamreza Abdi, Vaseem Raja, Mukul Machhindra Barwant, Ruchita Shrivastava

{"title":"Cell free systems for production of chemicals.","authors":"Sandeep Kaur, Gholamreza Abdi, Vaseem Raja, Mukul Machhindra Barwant, Ruchita Shrivastava","doi":"10.1016/bs.pmbts.2025.10.003","DOIUrl":"10.1016/bs.pmbts.2025.10.003","url":null,"abstract":"Modern technologies have also prompted biotechnologists to change their focus towards in vitro methods whereby biochemicals and biomaterials are prepared using cell-free conditions. Nevertheless, with many obstacles, the evolution of cell-free systems (CFSs) is thought to create additional opportunities in the creation of biologically-relevant molecules and materials. Cell-free biosynthesis serves to address significant discrepancies in traditional whole cell-based metabolic processes, and has a number of benefits, including the reduced structural and functional complexity, and the possibility to bypass cell viability problems and employ a controlled environment. These in vitro systems permit reconstitution of metabolic pathways with purified enzymes or crude lysates with rapid prototyping, precise control of reaction conditions and increased production of target compounds. The chapter presents a general overview of the design, optimization, and utilization of cell-free systems to prepare industrial chemicals, biofuels, pharmaceutical precursors, and specialty compounds. In this chapter, we explain the different categories of cell-free systems, like enzyme-based (PURE systems), lysate-based (TX-TL), and hybrid systems, that will be used to emphasize the functions of these systems in modular pathway construction, cofactor balancing, and energy regeneration. In addition, the synthesis of chemicals like isoprenoids, polyketides, organic acids, and aromatic compounds will also be a part of it. There is also an emphasis on synthetic biology tools, system engineering strategies, and scale-up techniques, which contribute to productivity and reduce production costs. The chapter is also intended to be read by the researchers, synthetic biologists, and industrial biotechnologists interested in sustainable biomanufacturing and synthetic biochemistry.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"219 ","pages":"107-146"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell-free systems for biotransformation. 生物转化的无细胞系统。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2025-10-11 DOI: 10.1016/bs.pmbts.2025.09.005

Huzaifa Ibrahim, Nimra Arshad, Hunaiza Fatima, Alvina Gul, Jayakumar Rajadas, Mustafeez Mujtaba Babar

{"title":"Cell-free systems for biotransformation.","authors":"Huzaifa Ibrahim, Nimra Arshad, Hunaiza Fatima, Alvina Gul, Jayakumar Rajadas, Mustafeez Mujtaba Babar","doi":"10.1016/bs.pmbts.2025.09.005","DOIUrl":"10.1016/bs.pmbts.2025.09.005","url":null,"abstract":"The cell-free systems based biotransformation has significantly transformed the field of biotechnology by facilitating the synthesis of therapeutic agents, biofuels and other commercially valuable chemicals. The current chapter initially focuses on presenting how the biotransformation process has conveniently transformed form the conventional cell-free based systems to modern cell-free protein synthesis (CFPS). This transformation has enabled the biomedical engineers and researchers to optimize the processes effectively. The chapter also looks into the three main biotransformation reactions i.e., enzymatic catalysis, redox transformation and hydrolytic processes while focusing on the optimization of pathways and processes that effectively enhance the modular design. The chapter also presents the practical benefits through various case studies in biofuel generation, synthesis of therapeutic proteins and eco-friendly manufacturing which ensures better yield, adaptability and reduction of unwanted substances in the industries. The chapter further illustrates the discussion on how cell-free systems have been designed and how the synthetic biology platforms outline the integration of machine learning and high throughput screening for the development of effective and efficient pathways. Furthermore, breakthroughs in eco-friendly chemistry, creation of artificial cells and synthetic biologicals ensure that the development of cell-free system is effective in biotransformation and is the fundamental basis for future production and advancements.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"219 ","pages":"147-170"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AI tools for cryo-EM: Protein particle picking, density map enhancement, and atomic model building. 用于低温电镜的人工智能工具：蛋白质颗粒拾取，密度图增强和原子模型构建。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2026-04-14 DOI: 10.1016/bs.pmbts.2026.03.009

Ashwin Dhakal, Rajan Gyawali, Joel Selvaraj, Jianlin Cheng

{"title":"AI tools for cryo-EM: Protein particle picking, density map enhancement, and atomic model building.","authors":"Ashwin Dhakal, Rajan Gyawali, Joel Selvaraj, Jianlin Cheng","doi":"10.1016/bs.pmbts.2026.03.009","DOIUrl":"10.1016/bs.pmbts.2026.03.009","url":null,"abstract":"Single-particle cryo-electron microscopy (cryo-EM) has rapidly evolved from largely manual, stepwise workflows to AI-assisted, increasingly automated protein structure determination pipelines. This chapter presents an end-to-end view on our deep learning-based AI tools that address three major stages of cryo-EM data analysis: protein particle picking, density map enhancement, and atomic structural model building. First, we introduce two of our AI-based particle pickers: CryoTransformer, a transformer-residual architecture trained on the large-scale CryoPPP dataset, and CryoSegNet, which couples a cryo-EM-specialized attention-gated U-Net with SAM to segment particles across diverse proteins and imaging conditions. Together, they deliver high precision-recall performance and improve downstream 3D reconstructions, outperforming widely used pickers on independent benchmarks. Second, we describe CryoTEN, a 3D UNETR++-style transformer to enhance cryo-EM density maps. On a 150-map test set, CryoTEN robustly improves local interpretability and downstream protein structure modeling while running>10× faster than other deep learning methods. Third, we present our two atomic protein model building frameworks: Cryo2Struct and MICA. Cryo2Struct is a fully automated de novo modeling framework that identifies atoms and residue types from density maps alone via a 3D transformer and assembles them into chains with a Hidden Markov Model, producing more complete and accurate models than other ab initio tools. MICA, a multimodal framework that integrates cryo-EM density maps with AlphaFold3 structure predictions at both input and output levels to further refine model accuracy and completeness, achieving near-experimental TM-scores on recently released high resolution density maps. Finally, we conclude by outlining open challenges and potential future directions in cryo-EM data analysis.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"223 ","pages":"71-113"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell-free systems for low-cost diagnostics. 低成本诊断的无细胞系统。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2025-09-20 DOI: 10.1016/bs.pmbts.2025.08.005

Rupal Dhariwal, Mukul Jain

{"title":"Cell-free systems for low-cost diagnostics.","authors":"Rupal Dhariwal, Mukul Jain","doi":"10.1016/bs.pmbts.2025.08.005","DOIUrl":"10.1016/bs.pmbts.2025.08.005","url":null,"abstract":"Cell-free systems have also become a revolutionary platform for low-cost diagnostics, providing fast, flexible, and scalable solutions to the conventional cell-based assays. Such systems, which utilize the fundamental biochemical machinery of cells without the intricacies of living organisms, have been of great use in point-of-care (POC) diagnostics, particularly in resource-poor environments. This chapter offers a broad overview of the basic principles, design approaches, and technological breakthroughs behind cell-free diagnostic development. It discusses the biochemical underpinnings of cell-free expression, such as ribosomal function, transcriptional control, and energy regeneration, with emphases on the leading platforms including E. coli lysates, wheat germ extracts, and PURE systems. The application of synthetic biology in the form of gene circuits, CRISPR-Cas tools, and RNA aptamers is presented here in the framework of improving the sensitivity and specificity of diagnostics. The chapter further discusses recent innovations in paper-based assays, microfluidic biosensors, and wearable biosensors, which are capable of offering real-time and field-deployable diagnostics. Major challenges in the form of reagent stability, scalability, and regulatory implications are analyzed carefully along with recent trends such as AI-based system design and personalization of diagnostics. In extensive case studies, the chapter highlights the promise of cell-free systems in filling diagnostic gaps, enhancing access to healthcare, and revolutionizing global health. This book strives to offer an encyclopedic sourcebook for researchers, clinicians, and innovators interested in bringing cell-free diagnostics forward.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"218 ","pages":"157-185"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell-free systems for expression of proteins and enzymes. 表达蛋白质和酶的无细胞系统。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2025-09-16 DOI: 10.1016/bs.pmbts.2025.08.002

Eeba, Jhalak Aggarwal, Nisheeth Agarwal

{"title":"Cell-free systems for expression of proteins and enzymes.","authors":"Eeba, Jhalak Aggarwal, Nisheeth Agarwal","doi":"10.1016/bs.pmbts.2025.08.002","DOIUrl":"10.1016/bs.pmbts.2025.08.002","url":null,"abstract":"Once restricted to cellular boundaries, cell-free expression has advanced to the forefront of contemporary biotechnology, heralding a novel paradigm in protein and enzyme biosynthesis. Cell-free expression system (CFES) offers an exquisite platform for production of these biomolecules in an open and controlled environment, liberated from the constraints of cellular regulations. The CFES facilitates precise manipulation of expression dynamics, thereby enabling the synthesis of proteins that are otherwise challenging to express in conventional hosts. Initially conceived as a pivotal tool for deciphering the genetic code, this technology has evolved into a sophisticated and versatile system for biosynthesis of proteins and enzymes, empowering researchers with unprecedented control over the molecular machinery of life. Biosynthesis of toxic proteins and complex enzymes in a flexible and highly regulated cell-free environment offers a panoply of applications in diagnostics, therapeutics, biomanufacturing and synthetic biology. From rudimentary extract-based systems to highly advanced and well-developed systems such as protein synthesis using recombinant elements (PURE), cell-free expression has profoundly reshaped the scientific landscape in ways that were previously unimaginable. Since the time of their inception, CFESs have elegantly exemplified the fusion of engineering and biological insights, thereby advancing the field from a technical curiosity to a treasure trove of possibilities. This chapter traces the journey of cell-free expression of proteins and enzymes followed by an extensive review of different types and formats of CFESs. Finally, the chapter ends by providing brief description of various applications, challenges and revolutionary promises that the cell-free systems behold for future.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"219 ","pages":"21-49"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent cryo-EM structures redefine the functional amyloid landscape. 最近的低温电镜结构重新定义了淀粉样蛋白的功能景观。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2026-04-02 DOI: 10.1016/bs.pmbts.2026.03.008

Salvador Ventura, Andrea Bartolomé-Nafría, Javier Garcia-Pardo

{"title":"Recent cryo-EM structures redefine the functional amyloid landscape.","authors":"Salvador Ventura, Andrea Bartolomé-Nafría, Javier Garcia-Pardo","doi":"10.1016/bs.pmbts.2026.03.008","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.03.008","url":null,"abstract":"Amyloids are traditionally associated with neurodegenerative and systemic diseases, yet it is now clear that they also perform essential physiological functions across kingdoms of life. Over the last decade, advances in cryogenic electron microscopy (cryo-EM) have enabled high-resolution structural characterization of functional amyloids, transforming our understanding of how the amyloid fold can be repurposed for biological activity. A landmark study in 2020 reported the cryo-EM structure of Orb2, a neuronal amyloid required for long-term memory persistence, establishing the first atomic view of a nuclear amyloid fibril. Subsequent structures of human RNA-binding proteins that form functional amyloids further expanded this paradigm. The structure of hnRNPDL-2 revealed how prion-like low-complexity domains can assemble into highly ordered, stable fibrils while keeping the necessary functionality for RNA metabolism. More recently, cryo-EM structures of the pigment-associated amyloid PMEL have provided insight into the molecular basis of melanosome biogenesis and pigmentation. In parallel, structural studies of bacterial functional amyloids, including the biofilm protein FapC, have uncovered architectures optimized for mechanical robustness and environmental resilience. Together, these pioneering studies reveal shared structural principles, alongside organism-specific adaptations that distinguish functional amyloids from their pathological counterparts.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"223 ","pages":"19-39"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing biological understanding of the poxvirus scaffold through breakthroughs in cryo-electron microscopy. 通过低温电子显微镜技术的突破，推进对痘病毒支架的生物学理解。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2026-04-02 DOI: 10.1016/bs.pmbts.2026.03.005

Seu-Na Lee, Jaekyung Hyun

{"title":"Advancing biological understanding of the poxvirus scaffold through breakthroughs in cryo-electron microscopy.","authors":"Seu-Na Lee, Jaekyung Hyun","doi":"10.1016/bs.pmbts.2026.03.005","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.03.005","url":null,"abstract":"Poxvirus morphogenesis involves extensive cellular membrane remodeling and assembly intermediates that have remained difficult to resolve at the molecular level. Progress in cryo-electron microscopy has been pivotal in characterization of immature poxvirus assembly by enabling direct visualization of scaffold architecture across scales. Structural analyses of in vitro assemblies revealed that the scaffold protein of vaccinia virus D13 forms a curved, honeycomb lattice through specific intertrimer interactions, structural features that promote spherical geometry. Cryo-electron tomography extended this understanding to a cellular context by resolving lattice organization and scaffold removal during maturation, and by revealing the emergence of an internal palisade layer that reshapes the condensing core. Together, these studies indicate that scaffold-mediated curvature, membrane coupling, and sequential lattice deployment define virion size and final architecture. Continued convergence of in vitro and in situ cryo-EM with correlative and time-resolved methods promises deeper understanding of transient intermediates and may guide strategies that target assembly pathways for antiviral intervention.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"223 ","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into the structure and diversity of the bacterial flagellum from cryo-EM studies. 从低温电镜研究中了解细菌鞭毛的结构和多样性。

3区生物学

Progress in molecular biology and translational science Pub Date : 2026-01-01 Epub Date: 2026-04-01 DOI: 10.1016/bs.pmbts.2026.03.002

Kailin Qin, Matías R Iglesias Rando, Julien R C Bergeron

{"title":"Insights into the structure and diversity of the bacterial flagellum from cryo-EM studies.","authors":"Kailin Qin, Matías R Iglesias Rando, Julien R C Bergeron","doi":"10.1016/bs.pmbts.2026.03.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.03.002","url":null,"abstract":"The bacterial flagellum is a large proteinaceous macromolecular machine that enables motility, host interaction, and virulence across bacterial species. Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) have reshaped our understanding of flagellar architecture, revealing near-atomic detail of core subcomplexes and extensive structural diversity beyond the canonical Salmonella system. Here we review the structure of the prototypical flagellum, including the basal body, export apparatus, motor complex, and extracellular hook-filament assembly, derived from recent cryo-EM studies. We compare species-specific adaptations such as sheathed and periplasmic flagella, extended basal body scaffolds, and variable stator arrangements that enable high-torque motility in different environments. We also synthesize the cryo-EM/cryo-ET experimental strategies used to stablish our current model of hierarchical flagellar assembly, emphasizing the coordination between secretion specificity switching, molecular rulers, and chaperone-mediated substrate targeting. Finally, we outline the major gaps in our understanding of motor mechanics, length control, regulatory factors governing flagellar number and localization, and the functional roles of accessory structures. Collectively, these advances illustrate how cryo-EM and cryo-ET guided structural biology is advancing our understanding of flagellar architecture, assembly, function and diversity.","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"223 ","pages":"179-202"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0