Trends in biotechnology最新文献

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Light-induced programmable solid-liquid phase transition of biomolecular condensates for improved biosynthesis.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-12 DOI: 10.1016/j.tibtech.2025.02.012
Ke Jin, Wenwen Yu, Yanfeng Liu, Jianghua Li, Guocheng Du, Jian Chen, Long Liu, Xueqin Lv
{"title":"Light-induced programmable solid-liquid phase transition of biomolecular condensates for improved biosynthesis.","authors":"Ke Jin, Wenwen Yu, Yanfeng Liu, Jianghua Li, Guocheng Du, Jian Chen, Long Liu, Xueqin Lv","doi":"10.1016/j.tibtech.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.012","url":null,"abstract":"<p><p>Keeping condensates in liquid-like states throughout the biosynthesis process in microbial cell factories remains an ongoing challenge. Here, we present a light-controlled phase regulator, which maintains the liquid-like features of synthetic condensates on demand throughout the biosynthesis process upon light induction, as demonstrated by various live cell-imaging techniques. Specifically, the tobacco etch virus (TEV) protease controlled by light cleaves intrinsically disordered proteins (IDPs) to alter their valency and concentration for controlled phase transition and programmable fluidity of cellular condensates. As a proof of concept, we harness this capability to significantly improve the production of squalene and ursolic acid (UA) in engineered Saccharomyces cerevisiae. Our work provides a powerful approach to program the solid-liquid phase transition of biomolecular condensates for improved biosynthesis.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SubtiToolKit: a bioengineering kit for Bacillus subtilis and Gram-positive bacteria.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-11 DOI: 10.1016/j.tibtech.2025.02.004
Joaquin Caro-Astorga, Matt Rogan, Koray Malcı, Hia Ming, Erika Debenedictis, Paul James, Tom Ellis
{"title":"SubtiToolKit: a bioengineering kit for Bacillus subtilis and Gram-positive bacteria.","authors":"Joaquin Caro-Astorga, Matt Rogan, Koray Malcı, Hia Ming, Erika Debenedictis, Paul James, Tom Ellis","doi":"10.1016/j.tibtech.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.004","url":null,"abstract":"<p><p>Building DNA constructs of increasing complexity is key to synthetic biology. Golden Gate (GG) methods led to the creation of cloning toolkits - collections of modular standardized DNA parts hosted on hierarchic plasmids, developed for yeast, plants, Gram-negative bacteria, and human cells. However, Gram-positive bacteria have been neglected. Bacillus subtilis is a Gram-positive model organism and a workhorse in the bioindustry. Here, we present the SubtiToolKit (STK), a high-efficiency cloning toolkit for B. subtilis and Gram-positive bacteria. Its design permits DNA constructs for transcriptional units (TUs), operons, and knockin and knockout applications. The STK contains libraries of promoters, ribosome-binding site (RBSs), fluorescent proteins, protein tags, terminators, genome integration parts, a no-leakage genetic device to control the expression of toxic products during Escherichia coli assembly, and a toolbox for industrially relevant strains of Geobacillus and Parageobacillus as an example of the STK versatility for other Gram-positive bacteria and its future perspective as a reference toolkit.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inducible regulating homologous recombination enables precise genome editing in Pichia pastoris without perturbing cellular fitness.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-11 DOI: 10.1016/j.tibtech.2025.02.005
Fan Bai, Peng Cai, Lun Yao, Yiwei Shen, Yunxia Li, Yongjin J Zhou
{"title":"Inducible regulating homologous recombination enables precise genome editing in Pichia pastoris without perturbing cellular fitness.","authors":"Fan Bai, Peng Cai, Lun Yao, Yiwei Shen, Yunxia Li, Yongjin J Zhou","doi":"10.1016/j.tibtech.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.005","url":null,"abstract":"<p><p>The methylotrophic yeast Pichia pastoris (also known as Komagataella pastoris) is an ideal host for producing proteins and natural products. Enhancing homologous recombination (HR) is helpful for improving the precision of genome editing, but results in stress to cellular fitness and is harmful for industrial applications. To overcome these challenges, we developed a tetracycline repressor protein (TetR)/tetO2 inducible system to dynamically regulate the HR-related gene RAD52 in P. pastoris. This approach significantly improved the positivity rate of single gene deletion to 81%. Furthermore, inducible overexpression of endogenous MUS81-MMS4 resulted in high-efficiency (81%) genome assembly of multiple genes. This inducible system had no adverse effect on cell growth in different media and resulted in greater fatty alcohol production from methanol compared with a strain constitutively overexpressing HR-related genes. We anticipate that this inducible regulation is applicable for enhancing HR for precise genome editing in P. pastoris and other non-conventional microbes without compromising cellular fitness.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
OMEGA-guided DNA polymerases enable random mutagenesis in a tunable window.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-11 DOI: 10.1016/j.tibtech.2025.02.011
Li-Hua Liu, Wei Lei, Zhiqian Zhang, Shijing Lai, Bo Xu, Qijun Ge, Jiawen Luo, Min Yang, Yang Zhang, Jinde Chen, Qiuru Zhong, Yi-Rui Wu, Ao Jiang
{"title":"OMEGA-guided DNA polymerases enable random mutagenesis in a tunable window.","authors":"Li-Hua Liu, Wei Lei, Zhiqian Zhang, Shijing Lai, Bo Xu, Qijun Ge, Jiawen Luo, Min Yang, Yang Zhang, Jinde Chen, Qiuru Zhong, Yi-Rui Wu, Ao Jiang","doi":"10.1016/j.tibtech.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.011","url":null,"abstract":"<p><p>Targeted random mutagenesis is crucial for breeding, directed evolution, and gene function studies, yet efficient tools remain scarce. Here, we present obligate mobile element guided activity (OMEGA)-R, an innovative targeted random mutagenesis system that integrates SpyCatcher-enIscB and PolI3M-TBD-SpyTag, outperforming existing state-of-the-art technologies in key metrics, such as protein size, mutagenesis efficiency, window length, and continuity. OMEGA-R achieves a dramatic enhancement of on-target mutagenesis, reaching a rate of 1.4 × 10<sup>-5</sup> base pairs (bp) per generation (bpg), with minimal off-target effects, in both Escherichia coli and Bacillus subtilis. The system also demonstrates exceptional compatibility with high-throughput screening (HTS) technologies, including fluorescence-activated droplet sorting (FADS) and phage-assisted continuous evolution (PACE). Utilizing OMEGA-R, we successfully identified a series of effective mutations within the T7 promoter (pT7), ribosome-binding site (RBS), superfolder GFP (sfGFP), and autocyclizing ribozyme (AR), which are invaluable for the development of high-performance biotechnology tools. These findings underscore the high efficiency and broad application potential of OMEGA-R.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering biological curvatures.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-10 DOI: 10.1016/j.tibtech.2025.02.013
Jiaxing Gong, Kejie Lu, Ying Qian, Yu Shrike Zhang, Mengfei Yu
{"title":"Engineering biological curvatures.","authors":"Jiaxing Gong, Kejie Lu, Ying Qian, Yu Shrike Zhang, Mengfei Yu","doi":"10.1016/j.tibtech.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.013","url":null,"abstract":"<p><p>The curvatures within the human body have essential functions, but their fabrication remains relatively unexplored. We re-emphasize the importance of curvatures in native biological tissues, present technologies to fabricate biomimetic curvatures, and discuss the challenges of integrating curvatures into biomanufacturing. Finally, we recommend how to incorporate curvatures into engineered tissues.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protein-based molecular imprinting: gelatin nanotraps for interleukin-6 sequestration in inflammation cell models.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-06 DOI: 10.1016/j.tibtech.2025.02.002
Alessandra Maria Bossi, Sofia Casella, Chiara Stranieri, Alice Marinangeli, Alessio Bucciarelli, Anna Maria Fratta Pasini, Devid Maniglio
{"title":"Protein-based molecular imprinting: gelatin nanotraps for interleukin-6 sequestration in inflammation cell models.","authors":"Alessandra Maria Bossi, Sofia Casella, Chiara Stranieri, Alice Marinangeli, Alessio Bucciarelli, Anna Maria Fratta Pasini, Devid Maniglio","doi":"10.1016/j.tibtech.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.002","url":null,"abstract":"<p><p>Protein-derived biomaterials are currently underrated as building blocks in molecular imprinting, even though they offer several benefits, such as biocompatibility and safe biodegradability. Gelatin is a biopolymer that can be easily modified with pendant double bonds for polymerization, making it suitable for tissue engineering and biofabrication. In this study, we used gelatin methacryloyl (GelMA) as a building block combined with molecular imprinting technology to create an original class of bioinspired nanotraps specifically capable of sequestering the proinflammatory cytokine interleukin-6 (IL-6). The stability in solution, biocompatibility, and biodegradability of the nanotraps were assessed. The nanotraps were selective and specific for IL-6, showing nanomolar affinity and, when tested in vitro on an inflammation cell model, sequestered IL-6 with a dose-response relationship. Overall, our study shows that protein chemistry-driven molecular imprinting could become more widely used to devise biocompatible functional nanomaterials.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in induced anhydrobiosis for cell and gamete storage.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-05 DOI: 10.1016/j.tibtech.2025.02.010
Pasqualino Loi, Luca Palazzese, Margherita Moncada, Martina Lo Sterzo, Domenico Iuso, Marta Czernik, Teruhiko Wakayama, Takahiro Kikawada
{"title":"Advances in induced anhydrobiosis for cell and gamete storage.","authors":"Pasqualino Loi, Luca Palazzese, Margherita Moncada, Martina Lo Sterzo, Domenico Iuso, Marta Czernik, Teruhiko Wakayama, Takahiro Kikawada","doi":"10.1016/j.tibtech.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.010","url":null,"abstract":"<p><p>It will appear strange to most readers, but lyophilization of spermatozoa was described by Chris Polge's first article that demonstrated the viability of spermatozoa stored in liquid nitrogen (LN<sub>2)</sub>. Since then, cryopreservation has become the only biobanking choice. The demonstration that lyophilized spermatozoa remain fertile has rekindled interest in noncryogenic biobanking. This perspective has recently been embraced by engineers, physicists, and anhydrobiotic physiologists, and their synergy has remarkably advanced the field. Progress in water subtraction procedures and dehydration medium formulated by biomimicking anhydrobiotic organisms has brought spermatozoa drying close to practical application for biodiversity preservation and human-assisted reproduction, allowing at the same time easy and safe transport of genetic resources on Earth and eventually space travel.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Large language model for knowledge synthesis and AI-enhanced biomanufacturing.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-05 DOI: 10.1016/j.tibtech.2025.02.008
Wenyu Li, Zhitao Mao, Zhengyang Xiao, Xiaoping Liao, Mattheos Koffas, Yixin Chen, Hongwu Ma, Yinjie J Tang
{"title":"Large language model for knowledge synthesis and AI-enhanced biomanufacturing.","authors":"Wenyu Li, Zhitao Mao, Zhengyang Xiao, Xiaoping Liao, Mattheos Koffas, Yixin Chen, Hongwu Ma, Yinjie J Tang","doi":"10.1016/j.tibtech.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.008","url":null,"abstract":"<p><p>Large language models (LLMs) are transforming synthetic biology (SynBio) education and research. In this review we cover the advancements and potential impacts of LLMs in biomanufacturing. First, we summarize recent developments and compare the capabilities of US and Chinese language models in addressing fundamental SynBio questions. Second, we discuss the application of LLMs in extracting SynBio information from unstructured data, constructing knowledge graphs, and enabling retrieval-augmented generation. Third, we anticipate that LLMs will not only revolutionize the design-build-test-learn (DBTL) cycle in metabolic modeling and engineering but also enable self-driving laboratories in future biomanufacturing. Finally, we emphasize the need for establishing benchmarks for LLMs, fostering trustworthy knowledge synthesis, developing biosecurity frameworks to prevent misuse, and encouraging collaboration among artificial intelligence (AI) scientists, SynBio researchers, and bioprocess engineers.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CarveAdornCurate: a versatile cloud-based platform for constructing multiscale metabolic models.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-04 DOI: 10.1016/j.tibtech.2025.01.011
Yang Cheng, Wenwen Yu, Xinyu Bi, Yanfeng Liu, Jianghua Li, Guocheng Du, Jian Chen, Xueqin Lv, Long Liu
{"title":"CarveAdornCurate: a versatile cloud-based platform for constructing multiscale metabolic models.","authors":"Yang Cheng, Wenwen Yu, Xinyu Bi, Yanfeng Liu, Jianghua Li, Guocheng Du, Jian Chen, Xueqin Lv, Long Liu","doi":"10.1016/j.tibtech.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.01.011","url":null,"abstract":"<p><p>Multiscale modeling is a promising approach for understanding cellular behaviors. However, existing multiscale modeling tools require meticulously curated genome-scale metabolic models (GEMs) as inputs, limiting the broad applications of multiscale models due to complex and time-consuming construction processes. To this end, we developed a novel workflow named CarveAdornCurate (CAC) for de novo multiscale modeling. The Carve module generates an ensemble of GEMs with strong genetic evidence, which is then upgraded to multiscale models using Adorn module. The Curate module was designed to find features important to the generated models. These three modules are integrated into a cloud-based platform to promote broad accessibility. As proof of concept, we constructed CAC-based multiscale models for Corynebacterium glutamicum and Yarrowia lipolytica, demonstrating their potential in guiding metabolic engineering. Overall, CAC is demonstrated to be an efficient and user-friendly tool for constructing multiscale models. It is available online at www.carveadorncurate.com/.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of animal and plant agricultural biotechnology.
IF 14.3 1区 工程技术
Trends in biotechnology Pub Date : 2025-03-01 DOI: 10.1016/j.tibtech.2024.11.003
Simona A Lubieniechi, Alison L Van Eenennaam, Stuart J Smyth
{"title":"Regulation of animal and plant agricultural biotechnology.","authors":"Simona A Lubieniechi, Alison L Van Eenennaam, Stuart J Smyth","doi":"10.1016/j.tibtech.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.tibtech.2024.11.003","url":null,"abstract":"<p><p>Fifty years ago, scientists developed a regulatory framework for the safe use of recombinant DNA that focused on potential biosafety risks associated with the products of genetic engineering (GE). This morphed into an expensive and lengthy premarket risk assessment requirement for GE agricultural biotechnology products triggered solely by the fact that modern molecular technologies were involved in the development of those products. This has limited the commercialization of GE crop products primarily to multinational enterprises and precluded the development of GE animals at scale. Gene editing offers an opportunity to rethink the regulation of agricultural biotechnologies, and several countries have determined that gene-edited products lacking any 'foreign' DNA will be treated in the same way as products of conventional breeding.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":"43 3","pages":"511-521"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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