Nature chemical biology最新文献_第8页

Massively parallel measurement of protein–protein interactions by sequencing using MP3-seq 利用 MP3-seq 测序技术大规模并行测量蛋白质与蛋白质之间的相互作用。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-27 DOI: 10.1038/s41589-024-01718-x

Alexandr Baryshev, Alyssa La Fleur, Benjamin Groves, Cirstyn Michel, David Baker, Ajasja Ljubetič, Georg Seelig

{"title":"Massively parallel measurement of protein–protein interactions by sequencing using MP3-seq","authors":"Alexandr Baryshev, Alyssa La Fleur, Benjamin Groves, Cirstyn Michel, David Baker, Ajasja Ljubetič, Georg Seelig","doi":"10.1038/s41589-024-01718-x","DOIUrl":"10.1038/s41589-024-01718-x","url":null,"abstract":"Protein–protein interactions (PPIs) regulate many cellular processes and engineered PPIs have cell and gene therapy applications. Here, we introduce massively parallel PPI measurement by sequencing (MP3-seq), an easy-to-use and highly scalable yeast two-hybrid approach for measuring PPIs. In MP3-seq, DNA barcodes are associated with specific protein pairs and barcode enrichment can be read by sequencing to provide a direct measure of interaction strength. We show that MP3-seq is highly quantitative and scales to over 100,000 interactions. We apply MP3-seq to characterize interactions between families of rationally designed heterodimers and to investigate elements conferring specificity to coiled-coil interactions. Lastly, we predict coiled heterodimer structures using AlphaFold-Multimer (AF-M) and train linear models on physics-based energy terms to predict MP3-seq values. We find that AF-M-based models could be valuable for prescreening interactions but experimentally measuring interactions remains necessary to rank their strengths quantitatively. A method called massively parallel PPI measurement by sequencing (MP3-seq) is developed for measuring protein–protein interactions at scale. MP3-seq uses DNA barcodes that are associated with specific protein pairs and provides a quantitative measure of interaction strength. Interactions between rationally designed heterodimers and elements conferring interaction specificity were investigated using MP3-seq.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1514-1523"},"PeriodicalIF":12.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis for intermodular communication in assembly-line polyketide biosynthesis 组装线多酮生物合成中模块间通信的结构基础

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-23 DOI: 10.1038/s41589-024-01709-y

Dillon P. Cogan, Alexander M. Soohoo, Muyuan Chen, Yan Liu, Krystal L. Brodsky, Chaitan Khosla

{"title":"Structural basis for intermodular communication in assembly-line polyketide biosynthesis","authors":"Dillon P. Cogan, Alexander M. Soohoo, Muyuan Chen, Yan Liu, Krystal L. Brodsky, Chaitan Khosla","doi":"10.1038/s41589-024-01709-y","DOIUrl":"https://doi.org/10.1038/s41589-024-01709-y","url":null,"abstract":"Assembly-line polyketide synthases (PKSs) are modular multi-enzyme systems with considerable potential for genetic reprogramming. Understanding how they selectively transport biosynthetic intermediates along a defined sequence of active sites could be harnessed to rationally alter PKS product structures. To investigate functional interactions between PKS catalytic and substrate acyl carrier protein (ACP) domains, we employed a bifunctional reagent to crosslink transient domain–domain interfaces of a prototypical assembly line, the 6-deoxyerythronolide B synthase, and resolved their structures by single-particle cryogenic electron microscopy (cryo-EM). Together with statistical per-particle image analysis of cryo-EM data, we uncovered interactions between ketosynthase (KS) and ACP domains that discriminate between intra-modular and inter-modular communication while reinforcing the relevance of conformational asymmetry during the catalytic cycle. Our findings provide a foundation for the structure-based design of hybrid PKSs comprising biosynthetic modules from different naturally occurring assembly lines.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"11 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042594","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

Degradable living plastics programmed by engineered spores 由工程孢子编程的可降解活塑料

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-21 DOI: 10.1038/s41589-024-01713-2

Chenwang Tang, Lin Wang, Jing Sun, Guangda Chen, Junfeng Shen, Liang Wang, Ying Han, Jiren Luo, Zhiying Li, Pei Zhang, Simin Zeng, Dianpeng Qi, Jin Geng, Ji Liu, Zhuojun Dai

{"title":"Degradable living plastics programmed by engineered spores","authors":"Chenwang Tang, Lin Wang, Jing Sun, Guangda Chen, Junfeng Shen, Liang Wang, Ying Han, Jiren Luo, Zhiying Li, Pei Zhang, Simin Zeng, Dianpeng Qi, Jin Geng, Ji Liu, Zhuojun Dai","doi":"10.1038/s41589-024-01713-2","DOIUrl":"https://doi.org/10.1038/s41589-024-01713-2","url":null,"abstract":"Plastics are widely used materials that pose an ecological challenge because their wastes are difficult to degrade. Embedding enzymes and biomachinery within polymers could enable the biodegradation and disposal of plastics. However, enzymes rarely function under conditions suitable for polymer processing. Here, we report degradable living plastics by harnessing synthetic biology and polymer engineering. We engineered Bacillus subtilis spores harboring the gene circuit for the xylose-inducible secretory expression of Burkholderia cepacia lipase (BC-lipase). The spores that were resilient to stresses during material processing were mixed with poly(caprolactone) to produce living plastics in various formats. Spore incorporation did not compromise the physical properties of the materials. Spore recovery was triggered by eroding the plastic surface, after which the BC-lipase released by the germinated cells caused near-complete depolymerization of the polymer matrix. This study showcases a method for fabricating green plastics that can function when the spores are latent and decay when the spores are activated and sheds light on the development of materials for sustainability.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"31 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013811","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

Polymers produced with depolymerase 用解聚酶生产的聚合物

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-20 DOI: 10.1038/s41589-024-01723-0

Russell Johnson

引用次数: 0

Lipids on the move 移动中的脂质

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-20 DOI: 10.1038/s41589-024-01725-y

Majda Bratovič

引用次数: 0

A pathway revisited 重新审视路径

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-20 DOI: 10.1038/s41589-024-01724-z

Gene Chong

引用次数: 0

Artificial boron enzymes 人工硼酶

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-16 DOI: 10.1038/s41589-024-01707-0

Xiao-Wang Chen, Zhiyu Bo, Yang Yang

引用次数: 0

Engineered IscB–ωRNA system with expanded target range for base editing 工程化 IscB-ωRNA 系统扩大了碱基编辑的目标范围

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-15 DOI: 10.1038/s41589-024-01706-1

Qingquan Xiao, Guoling Li, Dingyi Han, Haoqiang Wang, Mingyu Yao, Tingting Ma, Jingxing Zhou, Yu Zhang, Xiumei Zhang, Bingbing He, Yuan Yuan, Linyu Shi, Tong Li, Hui Yang, Jinhai Huang, Hainan Zhang

{"title":"Engineered IscB–ωRNA system with expanded target range for base editing","authors":"Qingquan Xiao, Guoling Li, Dingyi Han, Haoqiang Wang, Mingyu Yao, Tingting Ma, Jingxing Zhou, Yu Zhang, Xiumei Zhang, Bingbing He, Yuan Yuan, Linyu Shi, Tong Li, Hui Yang, Jinhai Huang, Hainan Zhang","doi":"10.1038/s41589-024-01706-1","DOIUrl":"https://doi.org/10.1038/s41589-024-01706-1","url":null,"abstract":"As the evolutionary ancestor of Cas9 nuclease, IscB proteins serve as compact RNA-guided DNA endonucleases and nickases, making them strong candidates for base editing. Nevertheless, the narrow targeting scope limits the application of IscB systems; thus, it is necessary to find more IscBs that recognize different target-adjacent motifs (TAMs). Here, we identified 10 of 19 uncharacterized IscB proteins from uncultured microbes with activity in mammalian cells. Through protein and ωRNA engineering, we further enhanced the activity of IscB ortholog IscB.m16 and expanded its TAM scope from MRNRAA to NNNGNA, resulting in a variant named IscB.m16*. By fusing the deaminase domains with IscB.m16* nickase, we generated IscB.m16*-derived base editors that exhibited robust base-editing efficiency in mammalian cells and effectively restored Duchenne muscular dystrophy proteins in diseased mice through single adeno-associated virus delivery. Thus, this study establishes a set of compact base-editing tools for basic research and therapeutic applications.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"30 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986326","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

Eating a way out of antibiotics 吃出抗生素

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01698-y

Felix Wong

引用次数: 0

Shifting redox reaction equilibria on demand using an orthogonal redox cofactor 利用正交氧化还原辅助因子按需改变氧化还原反应平衡

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01702-5

Derek Aspacio, Yulai Zhang, Youtian Cui, Emma Luu, Edward King, William B. Black, Sean Perea, Qiang Zhu, Yongxian Wu, Ray Luo, Justin B. Siegel, Han Li

{"title":"Shifting redox reaction equilibria on demand using an orthogonal redox cofactor","authors":"Derek Aspacio, Yulai Zhang, Youtian Cui, Emma Luu, Edward King, William B. Black, Sean Perea, Qiang Zhu, Yongxian Wu, Ray Luo, Justin B. Siegel, Han Li","doi":"10.1038/s41589-024-01702-5","DOIUrl":"10.1038/s41589-024-01702-5","url":null,"abstract":"Nature’s two redox cofactors, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), are held at different reduction potentials, driving catabolism and anabolism in opposite directions. In biomanufacturing, there is a need to flexibly control redox reaction direction decoupled from catabolism and anabolism. We established nicotinamide mononucleotide (NMN+) as a noncanonical cofactor orthogonal to NAD(P)+. Here we present the development of Nox Ortho, a reduced NMN+ (NMNH)-specific oxidase, that completes the toolkit to modulate NMNH:NMN+ ratio together with an NMN+-specific glucose dehydrogenase (GDH Ortho). The design principle discovered from Nox Ortho engineering and modeling is facilely translated onto six different enzymes to create NMN(H)-orthogonal biocatalysts with a consistent ~103–106-fold cofactor specificity switch from NAD(P)+ to NMN+. We assemble these enzymes to produce stereo-pure 2,3-butanediol in cell-free systems and in Escherichia coli, enabled by NMN(H)’s distinct redox ratio firmly set by its designated driving forces, decoupled from both NAD(H) and NADP(H). A metabolic system of engineered biocatalysts using the noncanonical cofactor nicotinamide mononucleotide is established for biomanufacturing in cell-free systems and in Escherichia coli without interference from nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1535-1546"},"PeriodicalIF":12.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974158","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