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":"37 ","pages":"Article 100499"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","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}
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":"37 ","pages":"Article 100501"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","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":"37 ","pages":"Article 100493"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","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":"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":"37 ","pages":"Article 100491"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","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}
{"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":"37 ","pages":"Article 100489"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","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":"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":"37 ","pages":"Article 100492"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","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":"Coupling between the cell cycle and the circadian clock: Lessons from computational modelling and consequences for cancer chronotherapy","authors":"Didier Gonze","doi":"10.1016/j.coisb.2024.100507","DOIUrl":"https://doi.org/10.1016/j.coisb.2024.100507","url":null,"abstract":"<div><p>Chronotherapy aims at optimising the time of day and dosing of drugs administration. This is a promising perspective because the toxicity and efficacy of many drugs show a dependence on the time of the day at which they are administrated. Efficient cancer chronotherapy requires a good understanding of the interplay between the cell cycle and the circadian clock. Computational models offer a way to study the dynamics resulting from the coupling between these two biological oscillators and to predict successful therapeutic protocols. We review here recent advances and highlight key challenges for further developments of predictive mathematical models.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"37 ","pages":"Article 100507"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139738774","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":"Recent development on DNA & genome synthesis","authors":"Wenfei Yu , Junbiao Dai , Yingxin Ma","doi":"10.1016/j.coisb.2023.100490","DOIUrl":"https://doi.org/10.1016/j.coisb.2023.100490","url":null,"abstract":"<div><p><span>After decades of development, DNA synthesis, assembly, and sequencing technologies have reached a high level, allowing faster and cheaper acquirements of synthetic genes or even </span><em>de novo</em><span> synthesis of an entire genome. Meanwhile, the value of synthetic genomes keeps increasing, and the target organisms have covered viruses, bacteria, and yeast and moved toward higher eukaryotes. However, as the length of genomes moves from kilobase to gigabase, the cost of synthetic genome projects increases sharply and requires years of effort to complete. Therefore, new DNA synthesis technology and a next-generation DNA synthesizer are urgently needed. In this review, we focus mainly on the advances in DNA and genome synthesis and discuss difficulties that need to be addressed in both areas.</span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"37 ","pages":"Article 100490"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570495","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":"Insertion sequences: Simple mobile elements with rich ecological and evolutionary structures","authors":"Yuki Kanai , Saburo Tsuru , Chikara Furusawa","doi":"10.1016/j.coisb.2023.100481","DOIUrl":"https://doi.org/10.1016/j.coisb.2023.100481","url":null,"abstract":"<div><p><span>Over the past two decades, genome sequencing has uncovered the diversity and distribution of insertion sequences within prokaryotic genomes. However, the complexity of insertion sequence ecology and evolution hinders us from understanding their nature. Recent studies have employed experimental and </span>computational models to study insertion sequences, emphasizing their role in shaping prokaryotic genome structures. Nonetheless, related areas remain with limited understanding, such as the speciation of insertion sequences. We believe that future studies should continue to develop tractable experimental and computational models to advance our understanding of IS ecology and evolution and their influence on the evolution of prokaryotic genomes.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"36 ","pages":"Article 100481"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50173552","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":"New faces of prokaryotic mobile genetic elements: Guide RNAs link transposition with host defense mechanisms","authors":"Eugene V. Koonin , Mart Krupovic","doi":"10.1016/j.coisb.2023.100473","DOIUrl":"10.1016/j.coisb.2023.100473","url":null,"abstract":"<div><p><span><span><span>Most life forms harbor multiple, diverse mobile genetic elements (MGE) that widely differ in their rates and mechanisms of mobility. Recent findings on two classes of MGE in </span>prokaryotes revealed a novel mechanism, RNA-guided transposition, where a transposon-encoded guide </span>RNA<span><span><span> directs the transposase to a unique site in the host genome. Tn7-like transposons, on multiple occasions, recruited </span>CRISPR systems that lost the capacity to cleave target </span>DNA<span> and instead mediate RNA-guided transposition via CRISPR RNA. Conversely, the abundant transposon-associated, RNA-guided nucleases IscB and TnpB that appear to promote proliferation of IS</span></span></span><em>200</em>/IS<em>605</em> and IS<em>607</em><span> transposons were the likely evolutionary ancestors of type II and type V CRISPR systems, respectively. Thus, RNA-guided target recognition is a major biological phenomenon that connects MGE with host defense mechanisms. More RNA-guided defensive and MGE-associated functionalities are likely to be discovered.</span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"36 ","pages":"Article 100473"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166361","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}