Nature biotechnology最新文献

Accelerating natural CO₂ removal from the atmosphere with ocean bacteria. 利用海洋细菌加速大气中二氧化碳的自然清除。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-03 DOI: 10.1038/s41587-026-03287-x

引用次数: 0

Engineered genomic attachment sites for site-specific recombinases enable high-efficiency integration in plants and human cells. 为位点特异性重组酶设计的基因组附着位点能够在植物和人类细胞中高效整合。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-02 DOI: 10.1038/s41587-026-03294-y

Linlin Yan, Lingyu Zhou, Qiang Gao, Lijuan Li, Lina Guo, Yidong Ran, Lixiao Zhang, Kang Zhang, Zhiwei Wang, Yan Li, Shengnan Li, Kevin Tianmeng Zhao

{"title":"Engineered genomic attachment sites for site-specific recombinases enable high-efficiency integration in plants and human cells.","authors":"Linlin Yan, Lingyu Zhou, Qiang Gao, Lijuan Li, Lina Guo, Yidong Ran, Lixiao Zhang, Kang Zhang, Zhiwei Wang, Yan Li, Shengnan Li, Kevin Tianmeng Zhao","doi":"10.1038/s41587-026-03294-y","DOIUrl":"https://doi.org/10.1038/s41587-026-03294-y","url":null,"abstract":"Here we developed a DNA-centric strategy for optimizing site-specific recombination by rationally engineering chimeric attachment sites. The high-activity att variants enhance Bxb1-mediated integration efficiency in human cells and plants. Among these att variants, the engineered attB(V111) site achieved 51.9% integration efficiency in HEK293T cells (1.7-fold versus wild-type attB) and 35.6% in rice protoplasts (4.4-fold versus wild-type attB). When paired with an engineered single protein mutant in the Bxb1 catalytic domain, the optimized system achieved targeted integration efficiencies of 31% for a CD19 chimeric antigen receptor cassette and 25% for an ornithine transcarbamylase expression cassette in human cells. In rice, these engineered variants enabled integration of a 5.8 kb herbicide-resistance cassette at a targeted genomic locus, with stable integration detected in 24% of regenerated plants. Oxford Nanopore-based long-read sequencing of edited plants reveals complete and precise insertion with high specificity. Propagation of edited seedlings to T1 plants confirms heritable editing to future generations. This approach provides a safe, broadly applicable approach for recombinase-based genome editing.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Machine learning interprets genome sequences to map possible microbial symbionts. 机器学习解释基因组序列以绘制可能的微生物共生体。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-02 DOI: 10.1038/s41587-026-03212-2

引用次数: 0

AI-enhanced adaptive virtual screening of large libraries for ligand discovery. 人工智能增强的大型文库自适应虚拟筛选，用于配体发现。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-01 DOI: 10.1038/s41587-026-03217-x

Domiziana Cecchini, AkshatKumar Nigam, Ming Tang, Joana Reis, Matt Koop, Andrea Gottinger, Callum Robert Nicoll, Yao Wang, Abhilash Jayaraj, Süleyman Selim Çınaroglu, Ricarda Törner, Yehor Malets, Minko Gehev, Krishna M Padmanabha Das, Kelly Churion, Jongwan Kim, Nidhin Thomas, Yong Li, Hyuk-Soo Seo, Sirano Dhe-Paganon, Christopher Secker, Mohammad Haddadnia, Alexander Hasson, Minkai Li, Abhishek Kumar, Roni Levin-Konigsberg, Eun-Bee Choi, Geoffrey I Shapiro, Huel Cox, Luke Sebastian, Chelsea Braithwaite, Puspalata Bashyal, Dmytro S Radchenko, Aditya Kumar, Lei Yang, Pierre-Yves Aquilanti, Henry Gabb, Amr Alhossary, Eric O'Neill, Gerhard Wagner, Alán Aspuru-Guzik, Yurii S Moroz, Charalampos G Kalodimos, Konstantin Fackeldey, John D Schuetz, Andrea Mattevi, Haribabu Arthanari, Christoph Gorgulla

{"title":"AI-enhanced adaptive virtual screening of large libraries for ligand discovery.","authors":"Domiziana Cecchini, AkshatKumar Nigam, Ming Tang, Joana Reis, Matt Koop, Andrea Gottinger, Callum Robert Nicoll, Yao Wang, Abhilash Jayaraj, Süleyman Selim Çınaroglu, Ricarda Törner, Yehor Malets, Minko Gehev, Krishna M Padmanabha Das, Kelly Churion, Jongwan Kim, Nidhin Thomas, Yong Li, Hyuk-Soo Seo, Sirano Dhe-Paganon, Christopher Secker, Mohammad Haddadnia, Alexander Hasson, Minkai Li, Abhishek Kumar, Roni Levin-Konigsberg, Eun-Bee Choi, Geoffrey I Shapiro, Huel Cox, Luke Sebastian, Chelsea Braithwaite, Puspalata Bashyal, Dmytro S Radchenko, Aditya Kumar, Lei Yang, Pierre-Yves Aquilanti, Henry Gabb, Amr Alhossary, Eric O'Neill, Gerhard Wagner, Alán Aspuru-Guzik, Yurii S Moroz, Charalampos G Kalodimos, Konstantin Fackeldey, John D Schuetz, Andrea Mattevi, Haribabu Arthanari, Christoph Gorgulla","doi":"10.1038/s41587-026-03217-x","DOIUrl":"https://doi.org/10.1038/s41587-026-03217-x","url":null,"abstract":"Ultralarge virtual screenings (ULVSs) evaluate billions of molecules for drug discovery but face cost, flexibility and scalability limits. We introduce AdaptiveFlow, an open-source platform that makes ULVSs more accessible, scalable and efficient and supports artificial intelligence (AI) and machine learning (ML) method development. AdaptiveFlow provides a screening-ready version of the Enamine REAL Space, to our knowledge the largest library of ready-to-dock, drug-like molecules, comprising 69 billion compounds, also available in SELFIES format. An 18-dimensional grid of molecular properties prioritizes promising chemical subspaces, with optional active learning, reducing computational costs by orders of magnitude. AdaptiveFlow integrates >1,500 docking protocols, including GPU-accelerated and ML-based methods, and achieves near-linear scaling on up to 5.6 million CPUs in the Amazon Web Services cloud. We identified nanomolar inhibitors of two disease-relevant targets, ferroptosis suppressor protein 1 (FSP1) and poly(ADP-ribose) polymerase 1. Co-crystal structures provided mechanistic insights into FSP1 inhibition. AdaptiveFlow enables drug discovery at unprecedented scale and supports the development of AI-driven methods.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Ensuring multiomics data reproducibility for artificial intelligence with reference materials as a common calibrator. 确保人工智能的多组学数据可重复性，参考物质作为通用校准器。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-01 DOI: 10.1038/s41587-026-03267-1

Leming Shi, Wenjun Bao, Aedín C Culhane, Xiang Fang, Cesare Furlanello, Ruixin Hao, Wendell D Jones, Rebecca Kusko, Samir Lababidi, Christopher E Mason, Andreas Scherer, Shraddha Thakkar, Weida Tong, Russell D Wolfinger, Joshua Xu, Ying Yu, Rui Zhang, Yuanting Zheng

引用次数: 0

A pervasive RT-qPCR artifact inflates RNA knockdown by RNA-targeting CRISPR. 一种普遍存在的RT-qPCR伪产物通过RNA靶向CRISPR使RNA敲低。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-01 DOI: 10.1038/s41587-026-03291-1

Leslie Watkins, Alan Zhu, Bin Wu

引用次数: 0

A genomic catalog of Earth's bacterial and archaeal symbionts. 地球细菌和古细菌共生体的基因组目录。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-31 DOI: 10.1038/s41587-026-03213-1

Juan C Villada, Yumary M Vasquez, Gitta Szabó, Ewan Whittaker-Walker, Miguel F Romero, Sarina Qin, Neha Varghese, Emiley A Eloe-Fadrosh, Nikos C Kyrpides, Axel Visel, Tanja Woyke, Frederik Schulz

{"title":"A genomic catalog of Earth's bacterial and archaeal symbionts.","authors":"Juan C Villada, Yumary M Vasquez, Gitta Szabó, Ewan Whittaker-Walker, Miguel F Romero, Sarina Qin, Neha Varghese, Emiley A Eloe-Fadrosh, Nikos C Kyrpides, Axel Visel, Tanja Woyke, Frederik Schulz","doi":"10.1038/s41587-026-03213-1","DOIUrl":"10.1038/s41587-026-03213-1","url":null,"abstract":"Microbial symbiosis drives the functional and phylogenomic diversification of life on Earth yet remains underexplored because of culturing challenges. This study used machine learning (ML) to predict symbiotic lifestyles in more than a hundred thousand microbial genomes from diverse environmental metagenome samples and reference genomes. Predictions were performed using symclatron, an ML framework developed to identify genomic signatures of symbionts. Predictions were deposited in a catalog we established called Symbiont Genomes (SymGs). The results indicate that 15-23% of uncultivated microorganisms likely engage in symbiotic relationships with other organisms, categorized as host-associated or obligate intracellular lifestyles, and are present in half of all known bacterial and archaeal phyla. We also identify genomic signatures of symbiotic lifestyles, including the loss of certain metabolic functions and the differential presence of metabolic modules that may enable host-dependent living. The symclatron software and the SymGs catalog represent valuable resources for studying symbioses, potentially facilitating future mechanistic investigations and engineering of host-microorganism associations.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Macropinocytosis-mediated recyclable LYTACs (McR-TACs) for receptor-independent protein degradation. 巨噬细胞介导的可回收LYTACs （McR-TACs）用于不依赖受体的蛋白质降解。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-31 DOI: 10.1038/s41587-026-03302-1

Peixin Liu, Yule Li, Tianyi Ma, Yawen You, Yu Chen, Michelle Y Cai, Quanyin Hu

{"title":"Macropinocytosis-mediated recyclable LYTACs (McR-TACs) for receptor-independent protein degradation.","authors":"Peixin Liu, Yule Li, Tianyi Ma, Yawen You, Yu Chen, Michelle Y Cai, Quanyin Hu","doi":"10.1038/s41587-026-03302-1","DOIUrl":"https://doi.org/10.1038/s41587-026-03302-1","url":null,"abstract":"The degradation of cell membrane and extracellular proteins with lysosome-targeting chimeras (LYTACs) is limited by nonrecyclable, receptor-dependent mechanisms that shuttle proteins to lysosomes, restricting the broad use of this emerging technology. Here we developed a recyclable chimera composed of a polyzwitterion and protein of interest (POI) ligand for protein degradation. This chimera could interact with the cell membrane to trigger macropinocytosis together with the POI in a receptor-independent manner. Furthermore, it can dissociate from the POI in the acidic endocytic compartments and subsequently be exocytosed through the endoplasmic reticulum-Golgi transcytosis pathway. Ultimately, the exocytotic chimera initiates the next round of targeted protein degradation. These macropinocytosis-mediated recyclable LYTACs (McR-TACs) durably degrade the cell membrane protein (programmed cell death ligand 1) or the extracellular protein (macrophage migration inhibitory factor) in a triple-negative breast cancer mouse model, thereby inhibiting the tumor growth. Collectively, McR-TACs show the potential of leveraging natural transport pathways to create recyclable protein degraders with wide-ranging applications.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Megascale microbiome analysis with DartUniFrac. 使用DartUniFrac进行大规模微生物组分析。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-28 DOI: 10.1038/s41587-026-03260-8

Jianshu Zhao, Daniel McDonald, Igor Sfiligoi, Manuel E Lladser, Lucas Patel, Yuhan Weng, Lora Khatib, Samuel Degregori, Antonio Gonzalez, Catherine A Lozupone, Rob Knight

引用次数: 0

Engineered bacterial siderophore production accelerates rock weathering for carbon removal. 工程细菌铁载体的产生加速了岩石的风化以去除碳。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-28 DOI: 10.1038/s41587-026-03288-w

Neil C Dalvie, Amogh P Jalihal, Abigail Fitzgibbon, Jan-Tobias Böhnke, Mohammed Hijaz, Quincey A Justman, Steven J Davis, Pamela A Silver, Michael Springer

{"title":"Engineered bacterial siderophore production accelerates rock weathering for carbon removal.","authors":"Neil C Dalvie, Amogh P Jalihal, Abigail Fitzgibbon, Jan-Tobias Böhnke, Mohammed Hijaz, Quincey A Justman, Steven J Davis, Pamela A Silver, Michael Springer","doi":"10.1038/s41587-026-03288-w","DOIUrl":"10.1038/s41587-026-03288-w","url":null,"abstract":"Silicate mineral weathering (dissolution) is a scalable strategy for capture and storage of CO2 but is too slow for industrial deployment. Bacteria can accelerate mineral dissolution by secreting siderophores, molecules that solubilize iron released from the mineral. Here we investigate how to deploy siderophore-producing bacteria at scale to continuously enhance dissolution of the mineral olivine. We demonstrate that natural genetic regulation precludes continuous siderophore production in mineral bioreactors. To overcome this limitation, we engineer the marine bacterium Alteromonas macleodii for enhanced siderophore production, conferring a 2.6-fold increase in the rate of olivine dissolution. Life-cycle analysis indicated that renewable feedstocks and minimal replenishment of modified cells are critical to achieve net CO2 removal at scale. With these guidelines, we constructed pilot-scale continuous mineral bioreactors that use unprocessed seawater and a renewable acetate feedstock to weather 4 kg of olivine. In reactors with engineered cells, we directly measured removal of 0.50 g CO2 per day from the air through alkalinity generation.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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