ACS Synthetic Biology最新文献_第3页

Tumor-Targeted Delivery of PD-1-Displaying Bacteriophages by Escherichia coli for Adjuvant Treatment of Colorectal Cancer.

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-02-10 DOI: 10.1021/acssynbio.4c00570

Hong-Rui Li, Ying Zhou, Bang-Ce Ye

{"title":"Tumor-Targeted Delivery of PD-1-Displaying Bacteriophages by Escherichia coli for Adjuvant Treatment of Colorectal Cancer.","authors":"Hong-Rui Li, Ying Zhou, Bang-Ce Ye","doi":"10.1021/acssynbio.4c00570","DOIUrl":"10.1021/acssynbio.4c00570","url":null,"abstract":"Bacteriophages, leveraging phage display and chemical modification, have the potential to deliver large payloads of antitumor agents with precision and to advance vaccine development. However, systemic phage administration often induces neutralizing antibodies, which accelerate phage clearance and reduce accumulation at the target site. To address this limitation, we propose a genetically modified nonpathogenic bacterial strain that specifically targets tumors and releases programmed death ligand 1 (PD-L1)-specific M13 bacteriophage within tumor tissue. We assessed the antitumor efficacy of this phage-expressing strain as an adjunctive therapeutic strategy along with a therapeutic bacterial strain engineered for the controlled release of an immunotoxin. The combination of these strains demonstrated synergistic effects in eliciting antitumor immune responses and inhibiting tumor growth in a murine model of colorectal cancer (CRC). Moreover, when combined with Folfox, the phage-expressing strain significantly extended the survival. This strategy of in vivo expression and tumor-specific release mediated by nonpathogenic bacterial strains provides an effective and safe method for targeted therapeutic phage delivery to tumors.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"407-419"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Solving Challenges in Microalgae-Based Living Materials

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 DOI: 10.1021/acssynbio.4c0068310.1021/acssynbio.4c00683

Friedrich Hans Kleiner*, Jeong-Joo Oh and Marie-Eve Aubin-Tam*,

{"title":"Solving Challenges in Microalgae-Based Living Materials","authors":"Friedrich Hans Kleiner*, Jeong-Joo Oh and Marie-Eve Aubin-Tam*, ","doi":"10.1021/acssynbio.4c0068310.1021/acssynbio.4c00683","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00683https://doi.org/10.1021/acssynbio.4c00683","url":null,"abstract":"Engineered living materials (ELMs) integrate aspects of material science and biology into a unique platform, leading to materials and devices with features of life. Among those, ELMs containing microalgae have received increased attention due to the many benefits photosynthetic organisms provide. Due to their relatively recent occurrence, photosynthetic ELMs still face many challenges related to reliability, lifetime, scalability, and more, often based on the complicated crosstalk of cellular, material-based, and environmental variables in time. This Viewpoint aims to summarize potential avenues for improving ELMs, beginning with an emphasis on understanding the cell’s perspective and the potential stresses imposed on them due to recurring flaws in many current ELMs. Potential solutions and their ease of implementation will be discussed, ranging from choice of organism, adjustments to the ELM design, to various genetic modification tools, so as to achieve ELMs with longer lifetime and improved functionality.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 2","pages":"307–315 307–315"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acssynbio.4c00683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Considerations for Domestication of Novel Strains of Filamentous Fungi.

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-01-30 DOI: 10.1021/acssynbio.4c00672

Randi M Pullen, Stephen R Decker, Venkataramanan Subramanian, Meaghan J Adler, Alexander V Tobias, Matthew Perisin, Christian J Sund, Matthew D Servinsky, Mark T Kozlowski

{"title":"Considerations for Domestication of Novel Strains of Filamentous Fungi.","authors":"Randi M Pullen, Stephen R Decker, Venkataramanan Subramanian, Meaghan J Adler, Alexander V Tobias, Matthew Perisin, Christian J Sund, Matthew D Servinsky, Mark T Kozlowski","doi":"10.1021/acssynbio.4c00672","DOIUrl":"10.1021/acssynbio.4c00672","url":null,"abstract":"Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"343-362"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Building the Future of Clinical Diagnostics: An Analysis of Potential Benefits and Current Barriers in CRISPR/Cas Diagnostics.

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-01-29 DOI: 10.1021/acssynbio.4c00816

Jeanne E van Dongen, Loes I Segerink

引用次数: 0

A Nitrate/Nitrite Biosensor Designed with an Antiterminator for In Vivo Diagnosis of Colitis Based on Bacteroides thetaiotaomicron. 基于 Bacteroides thetaiotaomicron 设计的用于体内诊断结肠炎的硝酸盐/亚硝酸盐生物传感器。

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-01-12 DOI: 10.1021/acssynbio.4c00602

Xiyuchen Yang, Meng Ye, Feng Wang, Xiaobing Yang, Xiangdong Gao, Juping Yu, Wei Liu

{"title":"A Nitrate/Nitrite Biosensor Designed with an Antiterminator for In Vivo Diagnosis of Colitis Based on Bacteroides thetaiotaomicron.","authors":"Xiyuchen Yang, Meng Ye, Feng Wang, Xiaobing Yang, Xiangdong Gao, Juping Yu, Wei Liu","doi":"10.1021/acssynbio.4c00602","DOIUrl":"10.1021/acssynbio.4c00602","url":null,"abstract":"Bacteroides thetaiotaomicron is a common microorganism in the human gut that has been linked to health benefits. Furthermore, it is an emerging synthetic biology chassis with the potential to be modified into diagnostic or therapeutic engineered probiotics. However, the absence of biological components limits its further applications. In this study, we developed an antiterminator microbial whole-cell biosensor (MWCB) based on B. thetaiotaomicron. The antiterminator-based element allows the chassis to detect colitis in mice by responding to nitrate and nitrite in an inflammatory environment. In particular, the nitrate/nitrite-inducible promoter was obtained by combining the constitutive promoter with the inducible terminator. Subsequently, the promoter and RBS were replaced to optimize a sensitive and specific response to nitrate/nitrite. A preliminary in vitro assessment was conducted to ascertain the functionality of the biosensor. Its in vivo sensing ability was evaluated in a chemically induced mouse model of ulcerative colitis (UC). The results demonstrated that the MWCB exhibited a robust response to colitis, with a notable positive correlation between the intensity of the response and the level of inflammation. This novel sensing element may provide a new avenue for the development of components for unconventional chassis, like B. thetaiotaomicron. It will also facilitate the development of engineered probiotics based on B. thetaiotaomicron, thereby providing patients with a wider range of medical treatment options.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"453-462"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Synthetic Dual-Input Hybrid Riboswitches─Optimized Genetic Regulators in Yeast.

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-02-04 DOI: 10.1021/acssynbio.4c00660

Daniel Kelvin, Janette Arias Rodriguez, Ann-Christin Groher, Kiara Petras, Beatrix Suess

{"title":"Synthetic Dual-Input Hybrid Riboswitches─Optimized Genetic Regulators in Yeast.","authors":"Daniel Kelvin, Janette Arias Rodriguez, Ann-Christin Groher, Kiara Petras, Beatrix Suess","doi":"10.1021/acssynbio.4c00660","DOIUrl":"10.1021/acssynbio.4c00660","url":null,"abstract":"Synthetic riboswitches, genetic regulatory elements composed entirely of RNA, have been engineered to control a variety of mechanisms at the level of both transcription and translation in all domains of life. The efficiency of riboswitch regulation can be increased by inserting two of them into an mRNA sequence in close proximity, resulting in a tandem riboswitch. The tandem state results in improved regulation beyond that of a single riboswitch by allowing both binding pockets to contribute to a higher dynamic range. The focus of this study was to create a novel tandem riboswitch design by integrating the binding pockets of two different riboswitches into one continuous structure, thereby creating a dual-input hybrid riboswitch. These hybrids remain compact in size with a shorter sequence length compared to a tandem riboswitch, while taking advantage of the binding pockets and scaffold sequences provided by both parental riboswitches. Through rational design, hybrid constructs derived from the combination of tetracycline-, tobramycin-, neomycin-, and paromomycin-binding riboswitches were engineered that significantly increase the dynamic range (e.g., from 14- to 36-fold for tobramycin) while increasing their expression levels in the absence of ligand (e.g., 28% to 68% expression for tetracycline). This study expands the toolbox of synthetic riboswitches and establishes general design guidelines applicable to similar riboswitches. Additionally, the dual-input state makes hybrid riboswitches an interesting target for the design of genetic regulators following Boolean logic.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"497-509"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Combined Transcriptomics and ¹³C Metabolomics Analysis Reveals pgi and edd Genes Involved in the Regulation of Efficient Cytidine Synthesis in Escherichia coli. 结合转录组学和13C代谢组学分析发现pgi和edd基因参与大肠杆菌胞苷高效合成的调控

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-01-19 DOI: 10.1021/acssynbio.4c00769

Lu Liu, Xiangjun Zhang, Tengteng Zhu, Tong Ye, Wei Ding, Huiyan Liu, Haitian Fang

{"title":"Combined Transcriptomics and 13C Metabolomics Analysis Reveals pgi and edd Genes Involved in the Regulation of Efficient Cytidine Synthesis in Escherichia coli.","authors":"Lu Liu, Xiangjun Zhang, Tengteng Zhu, Tong Ye, Wei Ding, Huiyan Liu, Haitian Fang","doi":"10.1021/acssynbio.4c00769","DOIUrl":"10.1021/acssynbio.4c00769","url":null,"abstract":"The development of an engineered strain for efficient cytidine production holds significant value for both research and industrial applications. In this study, the pgi and edd genes were knocked out to reveal their roles involved in the regulation of efficient cytidine synthesis in Escherichia coli. The results showed that after 36 h of shaking flask fermentation, the pgi knockout strain E. coli NXBG-14 produced a cytidine concentration of 2.57 ± 0.04 g/L, and the pgi and edd double knockout strain E. coli NXBG-15 produced a cytidine titer of 2.68 ± 0.03 g/L, which represented enhancements of 1.68 and 1.75 times over the start strain, respectively. Transcriptome analysis revealed that the differentially expressed genes (DEGs) in the NXBG-14 strain were mainly enriched in the glycolytic pathway and the tricarboxylic acid (TCA) cycle. Additionally, 13C metabolic flow distribution indicated a significant increase in 6-phosphogluconate in the pentose phosphate pathway (PPP) for NXBG-15. These findings suggest that modifications of the pgi and edd genes redirect central carbon metabolism and promote cytidine accumulation.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"542-552"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

De Novo Production of 1,6-Hexanediol and 1,6-Hexamethylenediamine from Glucose by Metabolic Engineered Escherichia coli.

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-02-12 DOI: 10.1021/acssynbio.4c00881

Nan Qin, Fanghuan Zhu, Youmeng Liu, Dehua Liu, Zhen Chen

{"title":"De Novo Production of 1,6-Hexanediol and 1,6-Hexamethylenediamine from Glucose by Metabolic Engineered Escherichia coli.","authors":"Nan Qin, Fanghuan Zhu, Youmeng Liu, Dehua Liu, Zhen Chen","doi":"10.1021/acssynbio.4c00881","DOIUrl":"10.1021/acssynbio.4c00881","url":null,"abstract":"1,6-Hexamethylenediamine (HMD) and 1,6-hexanediol (HDO) are pivotal C6 platform chemicals with extensive applications as key monomers in the synthesis of nylons, polyurethanes, and polyesters. The biological production of HMD and HDO from cheap and renewable bioresources represents an environmentally benign strategy for the sustainable chemical industry. Herein, we report the development of a novel biocatalytic route for the direct conversion of d-glucose to HMD and HDO in Escherichia coli. This was achieved through the integration of an adipic acid synthesis module with conversion modules tailored for HMD and HDO production. The study entailed a comprehensive optimization of pathway enzymes, protein expression, and precursor supply. Furthermore, a co-culture fermentation strategy was employed to enhance the efficiency of labor division, resulting in a two-strain cocultivation process that yielded 16.62 mg/L of HMD and 214.93 mg/L of HDO using glucose as the sole carbon source. This study establishes a foundational framework for the advancement of sustainable biological production processes for HMD and HDO from renewable resources.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"598-608"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Construction and Characterization of MoClo-Compatible Vectors for Modular Protein Expression in E. coli. 构建与表征用于大肠杆菌中模块化蛋白质表达的 MoClo 兼容载体。

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-01-12 DOI: 10.1021/acssynbio.4c00564

Jochem R Nielsen, Michael J Lewis, Wei E Huang

{"title":"Construction and Characterization of MoClo-Compatible Vectors for Modular Protein Expression in E. coli.","authors":"Jochem R Nielsen, Michael J Lewis, Wei E Huang","doi":"10.1021/acssynbio.4c00564","DOIUrl":"10.1021/acssynbio.4c00564","url":null,"abstract":"Cloning methods are fundamental to synthetic biology research. The capability to generate custom DNA constructs exhibiting predictable protein expression levels is crucial to the engineering of biology. Golden Gate cloning, a modular cloning (MoClo) technique, enables rapid and reliable one-pot assembly of genetic parts. In this study, we expand on the existing MoClo toolkits by constructing and characterizing compatible low- (p15A) and medium-copy (pBR322) destination vectors. Together with existing high-copy vectors, these backbones enable a protein expression range covering a 500-fold difference in normalized fluorescence output. We further characterize the expression- and burden profiles of each vector and demonstrate their use for the optimization of growth-coupled enzyme expression. The optimal expression of adhE (encoding alcohol dehydrogenase) for ethanol-dependent growth of Escherichia coli is determined using randomized Golden Gate Assembly, creating a diverse library of constructs with varying expression strengths and plasmid copy numbers. Through selective growth experiments, we show that relatively low expression levels of adhE facilitated optimal growth using ethanol as the sole carbon source, demonstrating the importance of adding low-copy vectors to the MoClo vector repertoire. This study emphasizes the importance of varying vector copy numbers in selection experiments to balance expression levels and burden, ensuring accurate identification of optimal conditions for growth. The vectors developed in this work are publicly available via Addgene (catalog #217582-217609).","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"398-406"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Do the Shuffle: Expanding the Synthetic Biology Toolkit for Shufflon-like Recombination Systems.

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-02-21 Epub Date: 2025-01-27 DOI: 10.1021/acssynbio.4c00790

Jan Katalinić, Morgan Richards, Alex Auyang, James H Millett, Manjunatha Kogenaru, Nikolai Windbichler

{"title":"Do the Shuffle: Expanding the Synthetic Biology Toolkit for Shufflon-like Recombination Systems.","authors":"Jan Katalinić, Morgan Richards, Alex Auyang, James H Millett, Manjunatha Kogenaru, Nikolai Windbichler","doi":"10.1021/acssynbio.4c00790","DOIUrl":"10.1021/acssynbio.4c00790","url":null,"abstract":"Naturally occurring DNA inversion systems play an important role in the generation of genetic variation and adaptation in prokaryotes. Shufflon invertase (SI) Rci from plasmid R64, recognizing asymmetric sfx sites, has been adopted as a tool for synthetic biology. However, the availability of a single enzyme with moderate rates of recombination has hampered the more widespread use of SIs. We identified 14 previously untested SI genes and their sfx sites in public databases. We established an assay based on single-molecule sequencing that allows the quantification of the inversion rates of these enzymes and determined cross-recognition to identify orthogonal SI/sfx pairs. We describe SI enzymes with substantially improved shuffling rates when expressed in an inducible manner in E. coli. Our findings will facilitate the use of SIs in engineering biology where synthetic shufflons enable the generation of millions of sequence variants in vivo for applications such as barcoding or experimental selection.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"363-372"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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