ACS Synthetic BiologyPub Date : 2025-07-18Epub Date: 2025-07-04DOI: 10.1021/acssynbio.5c00175
Weiming Lin, Haotian Yu, Weihao Li, Yemin Han, Manman Lv, Han Gao, Mengqing Cheng, Yan Huang, Kun Bi, Zuhong Lu, Quanjun Liu
{"title":"Scaling the High-Yield Potential of Large-Scale DNA Data Storage with Cap-Free DNA Synthesis.","authors":"Weiming Lin, Haotian Yu, Weihao Li, Yemin Han, Manman Lv, Han Gao, Mengqing Cheng, Yan Huang, Kun Bi, Zuhong Lu, Quanjun Liu","doi":"10.1021/acssynbio.5c00175","DOIUrl":"10.1021/acssynbio.5c00175","url":null,"abstract":"<p><p>DNA has emerged as a promising storage medium for addressing exponentially growing data storage demands, owing to its exceptional information density and chemical stability. However, current DNA synthesis techniques face significant limitations in achieving high-throughput data storage due to constrained synthesis yields. This study presents a novel high-yield cap-free synthesis (HYCFS) strategy that overcomes the limitations of conventional solid-phase phosphoramidite chemistry in both synthesis length and production yield. We established a theoretical product prediction model based on cap-free synthesis characteristics and systematically evaluated the strategy through standard DNA storage workflows. Under column-based synthesis conditions with high coupling efficiency (>99%), this approach demonstrated a 3-fold enhancement in effective sequence yield compared to traditional methods. Theoretical modeling predicts superior performance in array-based synthesis systems for large-scale data storage applications. HYCFS shows potential to enhance DNA-based data storage capacity by 2 orders of magnitude while reducing storage costs, thereby advancing the development of large-scale DNA data storage technologies.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2764-2773"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558398","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}
Jeffrey Chuong, Keaton W. Brown, Isaac Gifford, Dennis M. Mishler and Jeffrey E. Barrick*,
{"title":"","authors":"Jeffrey Chuong, Keaton W. Brown, Isaac Gifford, Dennis M. Mishler and Jeffrey E. Barrick*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646075","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}
Lauren M. Irie, Dylan M. Brown, Julius B. Lucks* and Nathan C. Gianneschi*,
{"title":"","authors":"Lauren M. Irie, Dylan M. Brown, Julius B. Lucks* and Nathan C. Gianneschi*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646076","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}
ACS Synthetic BiologyPub Date : 2025-07-18Epub Date: 2025-06-11DOI: 10.1021/acssynbio.4c00862
Davide Salzano, Barbara Shannon, Claire Grierson, Lucia Marucci, Nigel J Savery, Mario di Bernardo
{"title":"<i>In Vivo</i> Multicellular Feedback Control in Synthetic Microbial Consortia.","authors":"Davide Salzano, Barbara Shannon, Claire Grierson, Lucia Marucci, Nigel J Savery, Mario di Bernardo","doi":"10.1021/acssynbio.4c00862","DOIUrl":"10.1021/acssynbio.4c00862","url":null,"abstract":"<p><p>In this paper, we present a biomolecular control architecture able to guarantee stable and precise regulation of gene expression. Specifically, we engineer a microbial consortium comprising a cellular population, named <i>controllers</i>, that is tasked to regulate the expression of a gene in a second population, termed <i>targets</i>. Traditional biomolecular control strategies, while effective, are predominantly confined to single-cell applications, limiting their complexity and adaptability due to factors such as competition for limited cell resources and incompatible chemical reactions. Our approach overcomes these limitations by employing a distributed multicellular feedback loop between two strains of <i>Escherichia coli</i>, allowing for division of labor across the consortium. <i>In vivo</i> experiments demonstrate that this control system maintains precise and robust gene expression in the target population, even amid variations in consortium composition. Our study fills a critical gap in synthetic biology and paves the way for more complex and reliable applications in the field.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2537-2547"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273653","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}
ACS Synthetic BiologyPub Date : 2025-07-18Epub Date: 2025-06-17DOI: 10.1021/acssynbio.5c00120
Harman Mehta, Jose Jimenez, Rodrigo Ledesma-Amaro, Guy-Bart Stan
{"title":"Investigating the Potential of Division of Labor in Synthetic Bacterial Communities for the Production of Violacein.","authors":"Harman Mehta, Jose Jimenez, Rodrigo Ledesma-Amaro, Guy-Bart Stan","doi":"10.1021/acssynbio.5c00120","DOIUrl":"10.1021/acssynbio.5c00120","url":null,"abstract":"<p><p>With advancements in synthetic biology and metabolic engineering, microorganisms can now be engineered to perform increasingly complex functions, which may be limited by the resources available in individual cells. Introducing heterologous metabolic pathways introduces both genetic burden due to the competition for cellular transcription and translational machinery, as well as metabolic burden due to the redirection of metabolic flux from the native metabolic pathways. Division of labor in synthetic microbial communities offers a promising approach to enhance metabolic efficiency and resilience in bioproduction. By distributing complex metabolic pathways across multiple subpopulations, the resource competition and metabolic burden imposed on an individual cell are reduced, potentially enabling more efficient production of target compounds. Violacein is a high-value pigment with antitumor properties that exemplifies such a challenge due to its complex bioproduction pathway, imposing a significant metabolic burden on host cells. In this study, we investigated the benefits of division of labor for violacein production by splitting the violacein bioproduction pathway between two subpopulations of <i><i>Escherichia coli</i></i>-based synthetic communities. We tested several pathway splitting strategies and reported that splitting the pathway into two subpopulations expressing VioABE and VioDC at a final composition of 60:40 yields a 2.5-fold increase in violacein production as compared to a monoculture. We demonstrated that the coculture outperforms the monoculture when both subpopulations exhibit similar metabolic burden levels, resulting in comparable growth rates, and when both subpopulations are present in sufficiently high proportions.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2703-2709"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309247","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}
{"title":"Contemplating Bioproduction of Type-I Insect Sex Pheromones in <i>Saccharomyces cerevisiae</i>.","authors":"Shimin Wu, Xiao Lian, Xizhen Ge, Pingfang Tian","doi":"10.1021/acssynbio.5c00314","DOIUrl":"https://doi.org/10.1021/acssynbio.5c00314","url":null,"abstract":"<p><p>Insect sex pheromones (ISPs) can act as baits to trap heterosexual insects, representing a promising biocontrol strategy. However, current industrial production of ISPs relies largely on conventional chemical synthesis, which shows drawbacks, such as low yield and environmental pollution. Fortunately, remarkable progress in metabolic pathway engineering opens the possibility of biomanufacturing ISPs in microbial cell factories, which seems to be superior to chemical synthesis. While previous reviews have summarized pathways and enzymes related to the biosynthesis of ISPs, this review zeroes in on the enzymatic structures and catalytic mechanisms. In particular, we propose a potential pathway and discuss strategies for the heterologous biosynthesis of type-I ISPs in <i>Saccharomyces cerevisiae</i>, a suitable host for expressing enzymes, especially those requiring post-translational modifications. Overall, this review seeks to provide valuable insights for the complete biosynthesis of type-I ISPs.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663838","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}
ACS Synthetic BiologyPub Date : 2025-07-18Epub Date: 2025-07-02DOI: 10.1021/acssynbio.5c00209
Caiping Jiang, Kairui Zhai, R Clay Wright, Juhong Chen
{"title":"Engineered Yeasts Displaying PETase and MHETase as Whole-Cell Biocatalysts for the Degradation of Polyethylene Terephthalate (PET).","authors":"Caiping Jiang, Kairui Zhai, R Clay Wright, Juhong Chen","doi":"10.1021/acssynbio.5c00209","DOIUrl":"10.1021/acssynbio.5c00209","url":null,"abstract":"<p><p>Due to its low cost of manufacturing, poly(ethylene terephthalate) (PET, a polyester plastic) has been the most widely used plastic material for food packaging. However, PET is nonbiodegradable. It can take years to degrade when it is discarded into the environment. In recent years, plastic pollution has received much attention and has become a major environmental issue. In this study, we engineered yeast surfaces to display two PET-degrading enzymes (PETase and MHETase) to degrade PET plastics. The enzymes displayed on the yeast surface were characterized by using confocal microscopy and flow cytometry. The reaction conditions to degrade PET plastics using the engineered yeasts were optimal at pH 9 and 30 °C. In addition, the engineered yeasts showed great stability and reusability to degrade PET films. Furthermore, we demonstrated that the engineered yeasts as whole-cell catalysts can be used to degrade drinking water bottles into value-added products. This study provides a novel whole-cell biocatalyst using engineered yeasts to degrade plastic waste, offering a new strategy to solve plastic pollution and recycling challenges.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2810-2820"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551421","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}