Pub Date : 2025-11-19DOI: 10.1038/s44286-025-00303-w
Da Shen, Xin Wang, Yuan Gao, Wei Wang, Yuchao Li, He Chen, Yushuai Guo, Shuaihua Cao, Yuqing Huang, Yan Zhang, Chengzhi Wang, Shuyi Zhang
Current methods for protein engineering are constrained by limited understanding of sequence–function relationships, the difficulty of designing complex properties by artificial intelligence methods and labor-intensive directed evolution. Here, to enable continuous and scalable protein evolution and systematic exploration of protein adaptive landscapes, we established an industrial-grade automation platform featuring high throughput, high efficiency, enhanced reliability and minimal human intervention (operational for ~1 month). We then developed new genetic circuits for the OrthoRep continuous evolution system to achieve growth-coupled evolution for proteins with diverse and complex functionalities. This included improving lactate sensitivity of LldR via dual selection and increasing operator selectivity for LmrA using the NIMPLY circuit. We integrated these components into an all-in-one laboratory, iAutoEvoLab, and evolved proteins from inactive precursors to fully functional entities, such as a T7 RNA polymerase fusion protein CapT7 with mRNA capping properties, which can be directly applied to in vitro mRNA transcription and mammalian systems. Our system represents a versatile tool for protein engineering and expands the scope for investigating the origins and evolutionary trajectories of protein functions. This study reports on an industrial-grade, large-scale, all-in-one integrated and automated laboratory (iAutoEvoLab), combined with a genetic circuit-controlled, growth-coupled continuous evolution system based on OrthoRep, which can evolve proteins with diverse and complex functionalities. These include protein–protein interactions, protein–DNA interactions, proteins requiring both protein–DNA and protein–ligand interactions, and fusion proteins with low to near-zero activities.
{"title":"An industrial automated laboratory for programmable protein evolution","authors":"Da Shen, Xin Wang, Yuan Gao, Wei Wang, Yuchao Li, He Chen, Yushuai Guo, Shuaihua Cao, Yuqing Huang, Yan Zhang, Chengzhi Wang, Shuyi Zhang","doi":"10.1038/s44286-025-00303-w","DOIUrl":"10.1038/s44286-025-00303-w","url":null,"abstract":"Current methods for protein engineering are constrained by limited understanding of sequence–function relationships, the difficulty of designing complex properties by artificial intelligence methods and labor-intensive directed evolution. Here, to enable continuous and scalable protein evolution and systematic exploration of protein adaptive landscapes, we established an industrial-grade automation platform featuring high throughput, high efficiency, enhanced reliability and minimal human intervention (operational for ~1 month). We then developed new genetic circuits for the OrthoRep continuous evolution system to achieve growth-coupled evolution for proteins with diverse and complex functionalities. This included improving lactate sensitivity of LldR via dual selection and increasing operator selectivity for LmrA using the NIMPLY circuit. We integrated these components into an all-in-one laboratory, iAutoEvoLab, and evolved proteins from inactive precursors to fully functional entities, such as a T7 RNA polymerase fusion protein CapT7 with mRNA capping properties, which can be directly applied to in vitro mRNA transcription and mammalian systems. Our system represents a versatile tool for protein engineering and expands the scope for investigating the origins and evolutionary trajectories of protein functions. This study reports on an industrial-grade, large-scale, all-in-one integrated and automated laboratory (iAutoEvoLab), combined with a genetic circuit-controlled, growth-coupled continuous evolution system based on OrthoRep, which can evolve proteins with diverse and complex functionalities. These include protein–protein interactions, protein–DNA interactions, proteins requiring both protein–DNA and protein–ligand interactions, and fusion proteins with low to near-zero activities.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"685-698"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1038/s44286-025-00323-6
This Editorial showcases recent work on tandem reactor design, highlighting the nuanced role that reactor configuration can play in enabling efficient chemical transformations.
{"title":"One reactor, two reactor","authors":"","doi":"10.1038/s44286-025-00323-6","DOIUrl":"10.1038/s44286-025-00323-6","url":null,"abstract":"This Editorial showcases recent work on tandem reactor design, highlighting the nuanced role that reactor configuration can play in enabling efficient chemical transformations.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"665-665"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44286-025-00323-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1038/s44286-025-00298-4
Haobo Xu, Rong Yang
Haobo Xu and Rong Yang discuss how scaling laws and chemical engineering fundamentals help control the geometric precision of microdomes by transforming droplets into functional surfaces inspired by nature.
{"title":"Mastering microdomes via scaling laws","authors":"Haobo Xu, Rong Yang","doi":"10.1038/s44286-025-00298-4","DOIUrl":"10.1038/s44286-025-00298-4","url":null,"abstract":"Haobo Xu and Rong Yang discuss how scaling laws and chemical engineering fundamentals help control the geometric precision of microdomes by transforming droplets into functional surfaces inspired by nature.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"711-711"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1038/s44286-025-00310-x
Alessio Lavino
{"title":"Logic gates open to protein biosynthesis","authors":"Alessio Lavino","doi":"10.1038/s44286-025-00310-x","DOIUrl":"10.1038/s44286-025-00310-x","url":null,"abstract":"","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"668-668"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1038/s44286-025-00306-7
Gerard Prats Vergel, Huan Mu, Nikita Kolobov, Jasper Biemolt, David A. Vermaas, Thomas Burdyny
Bipolar membranes operated under reverse-bias (r-BPM) provide the only potential route to use anodes free of platinum group metals in CO2 electrolyzers when paired with the oxygen evolution reaction. Under 100% water dissociation efficiency (WDE) conditions, the OH− generated by a r-BPM fully replenishes the OH− consumed by the oxygen evolution reaction, maintaining an alkaline anolyte. However, unwanted co-ion crossover leads to <100% WDEs, gradually causing anolyte acidification and nickel-based anodes to corrode over time. Here we experimentally measured the WDE of r-BPMs in a membrane–electrode assembly configuration as a function of the current density, anolyte concentration and cation identity, finding that the highest measured WDE of 98% is insufficient to maintain an alkaline environment over extended operation. We further highlight through modeling that WDEs >99.8% are required to operate for >10,000 h with reasonable anolyte volumes. Our results show that r-BPMs CO2 electrolyzers require additional strategies, such as reverting to platinum group metal anodes or regenerating the anolyte, to operate stably at an industrial scale. Reverse-biased bipolar membranes can enable CO2 electrolysis with iridium-free anodes for extended durations, but only if 100% of the ionic charge is carried by water dissociation. Here, the authors show that practical systems fall far below unity water dissociation efficiencies, highlighting a performance gap for sustained alkaline operation using nickel-based anodes.
{"title":"Water dissociation efficiencies control the viability of reverse-bias bipolar membranes for CO2 electrolysis","authors":"Gerard Prats Vergel, Huan Mu, Nikita Kolobov, Jasper Biemolt, David A. Vermaas, Thomas Burdyny","doi":"10.1038/s44286-025-00306-7","DOIUrl":"10.1038/s44286-025-00306-7","url":null,"abstract":"Bipolar membranes operated under reverse-bias (r-BPM) provide the only potential route to use anodes free of platinum group metals in CO2 electrolyzers when paired with the oxygen evolution reaction. Under 100% water dissociation efficiency (WDE) conditions, the OH− generated by a r-BPM fully replenishes the OH− consumed by the oxygen evolution reaction, maintaining an alkaline anolyte. However, unwanted co-ion crossover leads to <100% WDEs, gradually causing anolyte acidification and nickel-based anodes to corrode over time. Here we experimentally measured the WDE of r-BPMs in a membrane–electrode assembly configuration as a function of the current density, anolyte concentration and cation identity, finding that the highest measured WDE of 98% is insufficient to maintain an alkaline environment over extended operation. We further highlight through modeling that WDEs >99.8% are required to operate for >10,000 h with reasonable anolyte volumes. Our results show that r-BPMs CO2 electrolyzers require additional strategies, such as reverting to platinum group metal anodes or regenerating the anolyte, to operate stably at an industrial scale. Reverse-biased bipolar membranes can enable CO2 electrolysis with iridium-free anodes for extended durations, but only if 100% of the ionic charge is carried by water dissociation. Here, the authors show that practical systems fall far below unity water dissociation efficiencies, highlighting a performance gap for sustained alkaline operation using nickel-based anodes.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"676-684"},"PeriodicalIF":0.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44286-025-00306-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1038/s44286-025-00307-6
Phase-separation-generated DNA condensates provide a versatile platform for building synthetic cells that mimic crowded intracellular environments. By integrating phase separation with DNA nanotechnology, we have programmed cytoskeleton growth inside synthetic cells. This growth provides switchable and orthogonal architectures that reinforce mechanical stability and can establish robust interfaces with living cells.
{"title":"Using DNA nanotubes to grow cytoskeletons in DNA-based synthetic cells","authors":"","doi":"10.1038/s44286-025-00307-6","DOIUrl":"10.1038/s44286-025-00307-6","url":null,"abstract":"Phase-separation-generated DNA condensates provide a versatile platform for building synthetic cells that mimic crowded intracellular environments. By integrating phase separation with DNA nanotechnology, we have programmed cytoskeleton growth inside synthetic cells. This growth provides switchable and orthogonal architectures that reinforce mechanical stability and can establish robust interfaces with living cells.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"672-673"},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1038/s44286-025-00299-3
Controlled depostion of amorphous zeolitic imidazolate framework (aZIF) films has proved challenging. Now, a spin-on deposition method is developed for aZIF films, enabling nanometer control of film thickness and uniformity at the wafer scale. Coupled with computational fluid dynamics simulations, this approach can be used to fabricate aZIF resists for advanced lithography applications.
{"title":"Chemical liquid deposition of amorphous zeolitic imidazolate framework resists","authors":"","doi":"10.1038/s44286-025-00299-3","DOIUrl":"10.1038/s44286-025-00299-3","url":null,"abstract":"Controlled depostion of amorphous zeolitic imidazolate framework (aZIF) films has proved challenging. Now, a spin-on deposition method is developed for aZIF films, enabling nanometer control of film thickness and uniformity at the wafer scale. Coupled with computational fluid dynamics simulations, this approach can be used to fabricate aZIF resists for advanced lithography applications.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 11","pages":"674-675"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1038/s44286-025-00300-z
In this Editorial, we outline our interest in biological systems research, highlighting how fundamental chemical engineering principles can help translate biophysical complexity into practical, transferable design strategies.
{"title":"The biophysics in our pages","authors":"","doi":"10.1038/s44286-025-00300-z","DOIUrl":"10.1038/s44286-025-00300-z","url":null,"abstract":"In this Editorial, we outline our interest in biological systems research, highlighting how fundamental chemical engineering principles can help translate biophysical complexity into practical, transferable design strategies.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 10","pages":"610-610"},"PeriodicalIF":0.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44286-025-00300-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145341935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1038/s44286-025-00295-7
Yanfei Zhu
{"title":"Making CO2 perform under pressure","authors":"Yanfei Zhu","doi":"10.1038/s44286-025-00295-7","DOIUrl":"10.1038/s44286-025-00295-7","url":null,"abstract":"","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 10","pages":"618-618"},"PeriodicalIF":0.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145341949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1038/s44286-025-00283-x
Keshia Saradima Indriadi, Sie Shing Wong, Peijie Han, Sikai Wang, Di Xu, Ning Yan
Ammonia decomposition is a key reaction in the green hydrogen economy because ammonia is an important carbon-free hydrogen carrier. In contrast to the prevalent focus on developing active catalysts to address the reaction’s slow kinetics at low temperatures, we introduce a tungsten wire lightbulb reactor that operates at unconventionally locally high temperatures while maintaining enhanced efficiency. Near the wire, the local temperature reaches up to 1,800 K, enabling ultrafast ammonia decomposition with rate constants much higher than those of leading catalysts under typical reaction conditions. Concurrently, the sharp temperature decrease along the radial direction allows for low power input, thus enhancing energy efficiency. The lightbulb reactor also realized up to 99.995% conversion at enhanced power input without the use of additional separation steps. We further propose a scaled-up reactor design that is two to three orders of magnitude smaller than current state-of-the-art reactors and highlight its potential applications within the emerging hydrogen economy. This study reports on a modular and scalable tungsten wire lightbulb reactor that achieves ultrafast ammonia decomposition by electrifying a tungsten wire to extremely high temperatures, increasing productivity without diminishing energy efficiency.
{"title":"Ultrafast ammonia decomposition using an electrified tungsten wire lightbulb reactor","authors":"Keshia Saradima Indriadi, Sie Shing Wong, Peijie Han, Sikai Wang, Di Xu, Ning Yan","doi":"10.1038/s44286-025-00283-x","DOIUrl":"10.1038/s44286-025-00283-x","url":null,"abstract":"Ammonia decomposition is a key reaction in the green hydrogen economy because ammonia is an important carbon-free hydrogen carrier. In contrast to the prevalent focus on developing active catalysts to address the reaction’s slow kinetics at low temperatures, we introduce a tungsten wire lightbulb reactor that operates at unconventionally locally high temperatures while maintaining enhanced efficiency. Near the wire, the local temperature reaches up to 1,800 K, enabling ultrafast ammonia decomposition with rate constants much higher than those of leading catalysts under typical reaction conditions. Concurrently, the sharp temperature decrease along the radial direction allows for low power input, thus enhancing energy efficiency. The lightbulb reactor also realized up to 99.995% conversion at enhanced power input without the use of additional separation steps. We further propose a scaled-up reactor design that is two to three orders of magnitude smaller than current state-of-the-art reactors and highlight its potential applications within the emerging hydrogen economy. This study reports on a modular and scalable tungsten wire lightbulb reactor that achieves ultrafast ammonia decomposition by electrifying a tungsten wire to extremely high temperatures, increasing productivity without diminishing energy efficiency.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 10","pages":"640-649"},"PeriodicalIF":0.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145341944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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