Simon Höllerer , Charlotte Desczyk , Ricardo Farrera Muro , Markus Jeschek
{"title":"From sequence to function and back – High-throughput sequence-function mapping in synthetic biology","authors":"Simon Höllerer , Charlotte Desczyk , Ricardo Farrera Muro , Markus Jeschek","doi":"10.1016/j.coisb.2023.100499","DOIUrl":"10.1016/j.coisb.2023.100499","url":null,"abstract":"<div><p>How does genetic sequence give rise to biological function? Answering this question is key to our understanding of life and the construction of synthetic biosystems that fight disease, resource scarcity and climate change. Unfortunately, the virtually infinite number of possible sequences and limitations in their functional characterization limit our current understanding of sequence-function relationships. To overcome this dilemma, several high-throughput methods to experimentally link sequences to corresponding functional properties have been developed recently. While all of these share the goal to collect sequence-function data at large scale, they differ significantly in their technical approach, functional readout and application scope. Herein, we highlight recent developments in the aspiring field of high-throughput sequence-function mapping providing a critical assessment of their potential in synthetic biology.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310023000562/pdfft?md5=50626ad0a0f676b1eece24dd590e5aca&pid=1-s2.0-S2452310023000562-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138993247","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}
{"title":"Accelerate acetogenic bioproduction: Acetogens as sustainable producers of biocommodities","authors":"Maximilian Flaiz , Diana Z. Sousa","doi":"10.1016/j.coisb.2023.100500","DOIUrl":"10.1016/j.coisb.2023.100500","url":null,"abstract":"<div><p>Gas fermentation using autotrophic acetogenic bacteria has been industrialized, however, its full potential remains untapped, with only native products like ethanol being produced thus far. Advancements in synthetic biology have enabled the recombinant production of diverse biocommodities to broaden their limited natural product spectrum from C1-gases. Additionally, co-culturing acetogens with other microorganisms holds the potential for expanding the product spectrum further. However, commercialization remains challenging due to complex pathway and (co)culturing optimizations. To address this, novel synthetic biology tools, including the use of high throughput biopart screenings using reporter proteins, the deployment of cell-free systems to combine best-performing enzymes, and the identification and elimination of competing pathways, can be employed. Incorporating genetically engineered strains in co-cultures improves dependencies, directs product formation, and increases resilience, enhancing bioproduction efficiency. This review emphasizes using these tools to enhance the recombinant production of biocommodities, offering promising solutions to overcome existing challenges.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310023000574/pdfft?md5=b34324e70ac5822168b823c24989c3e6&pid=1-s2.0-S2452310023000574-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139024556","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}
Wonhee Kim , Sohun Lee , Bong Hyun Sung , Jeong-Geol Na , Jeong Wook Lee
{"title":"Cell-free systems and genetic biosensors for accelerating enzyme and pathway prototyping","authors":"Wonhee Kim , Sohun Lee , Bong Hyun Sung , Jeong-Geol Na , Jeong Wook Lee","doi":"10.1016/j.coisb.2023.100501","DOIUrl":"10.1016/j.coisb.2023.100501","url":null,"abstract":"<div><p><span><span>Integration of cell-free systems with genetic biosensors is emerging as an advantageous platform for </span>small molecule<span> detection. This biosensor-coupled cell-free system simplifies an assay-and-detection procedure by combining the advantages of rapid and efficient protein expression through a cell-free system and the </span></span><em>in situ</em><span> detection capabilities provided by genetic biosensors. Moreover, this system is easy to assay multiple conditions at once, as the open environment of the cell-free systems enhances overall ease of handling. In this review, we focus on the acceleration of enzyme<span> and pathway prototyping using cell-free biosensors, as well as strategies to improve the sensitivity and specificity of biosensors. High-throughput screening tools that can expand the prototyping process by generating massive data sets for rapid evaluation were also described.</span></span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139021839","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}
Soo Young Moon , So-Hee Son , Seung-Ho Baek , Ju Young Lee
{"title":"Designing microbial cell factories for programmable control of cellular metabolism","authors":"Soo Young Moon , So-Hee Son , Seung-Ho Baek , Ju Young Lee","doi":"10.1016/j.coisb.2023.100493","DOIUrl":"10.1016/j.coisb.2023.100493","url":null,"abstract":"<div><p>Synthetic biology has promoted a conceptual shift in metabolic engineering for the microbial production of industrial chemicals toward a sustainable economy. Engineering principles from synthetic biology and metabolic engineering are integrated to redesign cellular metabolism to create microbial cell factories with emerging and programmable functionalities. Combining metabolic engineering with programmed spatial control is a promising approach that enables deep rewiring of microbial cell factory metabolism for the efficient production of bio-based chemicals. In this review, we discuss metabolic compartmentalization approaches for programmable control of cellular metabolism, including intracellular or intercellular partitioning-based organization of biosynthetic pathways. We also examine the designs and applications of cellular compartments and their analogs, highlighting selected examples for creating efficient and sustainable microbial cell factories.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310023000501/pdfft?md5=4b2c73384af314ae39010dd8a4898183&pid=1-s2.0-S2452310023000501-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138609855","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}
{"title":"Editorial Board Page","authors":"","doi":"10.1016/S2452-3100(23)00052-5","DOIUrl":"https://doi.org/10.1016/S2452-3100(23)00052-5","url":null,"abstract":"","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310023000525/pdfft?md5=796aff2b175ba2c293085564fefc486e&pid=1-s2.0-S2452310023000525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489626","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}
Dominic K. Devlin , Austen R.D. Ganley , Nobuto Takeuchi
{"title":"A pan-metazoan view of germline-soma distinction challenges our understanding of how the metazoan germline evolves","authors":"Dominic K. Devlin , Austen R.D. Ganley , Nobuto Takeuchi","doi":"10.1016/j.coisb.2023.100486","DOIUrl":"10.1016/j.coisb.2023.100486","url":null,"abstract":"<div><p>A germline-soma distinction — irreversible differentiation from reproductive germline cells to sterile somatic cells — is a landmark of cellular cooperation in metazoans. Traditionally, this distinction was considered a property of only some metazoan taxa, such as vertebrates and insects. However, recent studies on a number of other metazoan taxa are challenging this traditional perspective, suggesting that a germline-soma distinction is widespread among metazoans. Here, we review recent molecular and cellular evidence supporting this suggestion and emphasise the difference between germline-soma distinction and germline segregation. We also outline the considerable diversity among metazoans in germline specification, segregation and regeneration. We finish by discussing how evolutionary explanations for this diversity can be investigated by harnessing theoretical modelling approaches.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310023000434/pdfft?md5=06baf838b4701fd9a8bb16f2bc11278d&pid=1-s2.0-S2452310023000434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135668926","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}
{"title":"Engineering live bacterial therapeutics to treat human diseases","authors":"In Young Hwang","doi":"10.1016/j.coisb.2023.100492","DOIUrl":"https://doi.org/10.1016/j.coisb.2023.100492","url":null,"abstract":"<div><p>In recent years, synthetic biology has provided many engineering approaches to reprogram and engineer cells in diverse applications including the development of novel therapeutics. Engineered cells provide advantages over small molecules<span> or biologics, as these cells can be reprogrammed to have spatial and temporal control over the delivery of therapeutics in response to disease biomarkers. Herein, some of the recent applications of engineered live bacterial therapeutics against human diseases such as cancer, metabolic disorders<span>, gastrointestinal diseases, and infections are reviewed. Furthermore, this review highlights active clinical trials on engineered cells with promising results.</span></span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138769941","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}
{"title":"Construction of microbial platform chassis for CO2 utilisation","authors":"Simona Della Valle, Weiming Tu, Wei E. Huang","doi":"10.1016/j.coisb.2023.100489","DOIUrl":"https://doi.org/10.1016/j.coisb.2023.100489","url":null,"abstract":"<div><p>To achieve a circular bioeconomy, carbon streams can be utilised through microbial conversion to produce value-added compounds. Although some microorganisms are naturally able to grow on these renewable carbon sources and generate desirable molecules, significant engineering is required to develop platform chassis exhibiting attractive performance parameters for industrial-scale processes. Here, we provide a brief overview of the core considerations in chassis engineering for autotrophic bioproduction, including carbon and energy supply, in addition to emerging standards for rewiring metabolic pathways to enhance growth and biosynthetic capabilities. We highlight examples of successful strategies, placing emphasis on recent advances in engineering autotrophic capabilities in both native autotrophs and heterotrophs.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245231002300046X/pdfft?md5=7a85534cbab719644d59ae9349c85905&pid=1-s2.0-S245231002300046X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138582140","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}
{"title":"Systems metabolic engineering for the production of pharmaceutical natural products","authors":"Hengrui Zhou , Hyunmin Eun , Sang Yup Lee","doi":"10.1016/j.coisb.2023.100491","DOIUrl":"https://doi.org/10.1016/j.coisb.2023.100491","url":null,"abstract":"<div><p>The increased awareness of the pharmaceutical supply chain<span><span> issues after the recent pandemic crisis has emphasized the need for innovative drug discovery. Natural products (NPs) have emerged as promising candidates to address pandemics due to their diverse structures and medicinal properties. However, development of novel NP-drugs in pharmaceutical supply chains has faced many challenges, including the absence of an efficient large-scale production platform to meet market demands. The advent of systems metabolic engineering has facilitated the efficient production of NPs in microorganisms compared with traditional plant-based and chemical-based production. In this article, we review recent strategies in systems metabolic engineering that have opened up new avenues for NP-drug discovery and production. In addition, we suggest viewpoints on how </span>combinatorial approaches of systems metabolic engineering and synthetic chemistry will further enhance the diversity of NP-drugs and provide prospects for the development of NP-drugs in the pharmaceutical supply chain.</span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138582331","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}
Amir Bitran , William M. Jacobs , Eugene Shakhnovich
{"title":"The critical role of co-translational folding: An evolutionary and biophysical perspective","authors":"Amir Bitran , William M. Jacobs , Eugene Shakhnovich","doi":"10.1016/j.coisb.2023.100485","DOIUrl":"https://doi.org/10.1016/j.coisb.2023.100485","url":null,"abstract":"<div><p><span>Many proteins begin to fold as they are being synthesized by the ribosome. Growing experimental evidence, supported by new theory, simulation and bioinformatics studies, suggests that many proteins rely on co-translational folding in order to fold efficiently and to avoid misfolded intermediates that arise posttranslationally. Consistent with these findings, complementary bioinformatics analyses have revealed widespread evolutionary selection for efficient co-translational folding kinetics. This perspective summarizes recent theoretical and experimental advances that have uncovered specific molecular mechanisms underlying the benefits of co-translational folding </span><em>in vivo</em>. We highlight studies involving single-domain proteins that begin adopting nativelike structure on the ribosome, which can help commit misfolding-prone domains to their native state. We emphasize the need for new experimental techniques to probe the molecular details underlying this process systematically.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570230","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}