{"title":"Chemical reaction networks for computing logarithm.","authors":"Chun Tung Chou","doi":"10.1093/synbio/ysx002","DOIUrl":"10.1093/synbio/ysx002","url":null,"abstract":"<p><p>Living cells constantly process information from their living environment. It has recently been shown that a number of cell signaling mechanisms (e.g. G protein-coupled receptor and epidermal growth factor) can be interpreted as computing the logarithm of the ligand concentration. This suggests that logarithm is a fundamental computation primitive in cells. There is also an increasing interest in the synthetic biology community to implement analog computation and computing the logarithm is one such example. The aim of this article is to study how the computation of logarithm can be realized using chemical reaction networks (CRNs). CRNs cannot compute logarithm exactly. A standard method is to use power series or rational function approximation to compute logarithm approximately. Although CRNs can realize these polynomial or rational function computations in a straightforward manner, the issue is that in order to be able to compute logarithm accurately over a large input range, it is necessary to use high-order approximation that results in CRNs with a large number of reactions. This article proposes a novel method to compute logarithm accurately in CRNs while keeping the number of reactions in CRNs low. The proposed method can create CRNs that can compute logarithm to different levels of accuracy by adjusting two design parameters. In this article, we present the chemical reactions required to realize the CRNs for computing logarithm. The key contribution of this article is a novel method to create CRNs that can compute logarithm accurately over a wide input range using only a small number of chemical reactions.</p>","PeriodicalId":74902,"journal":{"name":"Synthetic biology (Oxford, England)","volume":"2 1","pages":"ysx002"},"PeriodicalIF":0.0,"publicationDate":"2017-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/42/ysx002.PMC7513738.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38532910","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}
Hiroyuki Kuwahara, Ramzan Umarov, Islam Almasri, Xin Gao
{"title":"ACRE: Absolute concentration robustness exploration in module-based combinatorial networks.","authors":"Hiroyuki Kuwahara, Ramzan Umarov, Islam Almasri, Xin Gao","doi":"10.1093/synbio/ysx001","DOIUrl":"https://doi.org/10.1093/synbio/ysx001","url":null,"abstract":"<p><p>To engineer cells for industrial-scale application, a deep understanding of how to design molecular control mechanisms to tightly maintain functional stability under various fluctuations is crucial. Absolute concentration robustness (ACR) is a category of robustness in reaction network models in which the steady-state concentration of a molecular species is guaranteed to be invariant even with perturbations in the other molecular species in the network. Here, we introduce a software tool, absolute concentration robustness explorer (ACRE), which efficiently explores combinatorial biochemical networks for the ACR property. ACRE has a user-friendly interface, and it can facilitate efficient analysis of key structural features that guarantee the presence and the absence of the ACR property from combinatorial networks. Such analysis is expected to be useful in synthetic biology as it can increase our understanding of how to design molecular mechanisms to tightly control the concentration of molecular species. ACRE is freely available at https://github.com/ramzan1990/ACRE.</p>","PeriodicalId":74902,"journal":{"name":"Synthetic biology (Oxford, England)","volume":"2 1","pages":"ysx001"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/synbio/ysx001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38532909","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}
Thomas C Williams, Xin Xu, Martin Ostrowski, Isak S Pretorius, Ian T Paulsen
{"title":"Positive-feedback, ratiometric biosensor expression improves high-throughput metabolite-producer screening efficiency in yeast.","authors":"Thomas C Williams, Xin Xu, Martin Ostrowski, Isak S Pretorius, Ian T Paulsen","doi":"10.1093/synbio/ysw002","DOIUrl":"10.1093/synbio/ysw002","url":null,"abstract":"<p><p>Biosensors are valuable and versatile tools in synthetic biology that are used to modulate gene expression in response to a wide range of stimuli. Ligand responsive transcription factors are a class of biosensor that can be used to couple intracellular metabolite concentration with gene expression to enable dynamic regulation and high-throughput metabolite producer screening. We have established the <i>Saccharomyces cerevisiae WAR1</i> transcriptional regulator and <i>PDR12</i> promoter as an organic acid biosensor that can be used to detect varying levels of para-hydroxybenzoic acid (PHBA) production from the shikimate pathway and output green fluorescent protein (GFP) expression in response. The dynamic range of GFP expression in response to PHBA was dramatically increased by engineering positive-feedback expression of the <i>WAR1</i> transcriptional regulator from its target <i>PDR12</i> promoter. In addition, the noise in GFP expression at the population-level was controlled by normalising GFP fluorescence to constitutively expressed mCherry fluorescence within each cell. These biosensor modifications increased the high-throughput screening efficiency of yeast cells engineered to produce PHBA by 5,000-fold, enabling accurate fluorescence activated cell sorting isolation of producer cells that were mixed at a ratio of 1 in 10,000 with non-producers. Positive-feedback, ratiometric transcriptional regulator expression is likely applicable to many other transcription-factor/promoter pairs used in synthetic biology and metabolic engineering for both dynamic regulation and high-throughput screening applications.</p>","PeriodicalId":74902,"journal":{"name":"Synthetic biology (Oxford, England)","volume":"2 1","pages":"ysw002"},"PeriodicalIF":0.0,"publicationDate":"2017-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/4d/ysw002.PMC7513737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38532908","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":"<i>Synthetic Biology</i>: fostering the cyber-biological revolution.","authors":"Jean Peccoud","doi":"10.1093/synbio/ysw001","DOIUrl":"https://doi.org/10.1093/synbio/ysw001","url":null,"abstract":"<p><p>Since the description, in 2000, of two artificial gene networks, synthetic biology has emerged as a new engineering discipline that catalyzes a change of culture in the life sciences. Recombinant DNA can now be fabricated rather than cloned. Instead of focusing on the development of ad-hoc assembly strategies, molecular biologists can outsource the fabrication of synthetic DNA molecules to a network of DNA foundries. Model-driven product development cycles that clearly identify design, build, and test phases are becoming as common in the life sciences as they have been in other engineering fields. A movement of citizen scientists with roots in community labs throughout the world is trying to democratize genetic engineering. It challenges the life science establishment just like visionaries in the 70s advocated that computing should be personal at a time when access to computers was mostly the privilege of government scientists. Synthetic biology is a cultural revolution that will have far reaching implications for the biotechnology industry. The work of synthetic biologists today prefigures a new generation of cyber-biological systems that may to lead to the 5<sup>th</sup> industrial revolution. By catering to the scientific publishing needs of all members of a diverse community, <i>Synthetic Biology</i> hopes to do its part to support the development of this new engineering discipline, catalyze the culture changes it calls for, and foster the development of a new industry far into the twenty first century.</p>","PeriodicalId":74902,"journal":{"name":"Synthetic biology (Oxford, England)","volume":"1 1","pages":"ysw001"},"PeriodicalIF":0.0,"publicationDate":"2016-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/synbio/ysw001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38532907","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}