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dc.contributor.authorWan, Xia
dc.contributor.authorMarsafari, Monireh
dc.contributor.authorXu, Peng
dc.date.accessioned2019-04-12T16:32:19Z
dc.date.available2019-04-12T16:32:19Z
dc.date.issued2019-03-26
dc.description.abstractNature has evolved exquisite sensing mechanisms to detect cellular and environmental signals surrounding living organisms. These biosensors have been widely used to sense small molecules, detect environmental cues and diagnose disease markers. Metabolic engineers and synthetic biologists have been able to exploit metabolites-responsive transcriptional factors (MRTFs) as basic tools to rewire cell metabolism, reprogram cellular activity as well as boost cell’s productivity. This is commonly achieved by integrating sensor-actuator systems with biocatalytic functions and dynamically allocating cellular resources to drive carbon flux toward the target pathway. Up to date, most of identified MRTFs are derived from bacteria. As an endeavor to advance intelligent biomanufacturing in yeast cell factory, we will summarize the opportunities and challenges to transfer the bacteria-derived MRTFs to expand the small-molecule sensing capability in eukaryotic cells. We will discuss the design principles underlying MRTF-based biosensors in eukaryotic cells, including the choice of reliable reporters and the characterization tools to minimize background noise, strategies to tune the sensor dynamic range, sensitivity and specificity, as well as the criteria to engineer activator and repressor-based biosensors. Due to the physical separation of transcription and protein expression in eukaryotes, we argue that nuclear import/export mechanism of MRTFs across the nuclear membrane plays a critical role in regulating the MRTF sensor dynamics. Precisely-controlled MRTF response will allow us to repurpose the vast majority of transcriptional factors as molecular switches to achieve temporal or spatial gene expression in eukaryotes. Uncovering this knowledge will inform us fundamental design principles to deliver robust cell factories and enable the design of reprogrammable and predictable biological systems for intelligent biomanufacturing, smart therapeutics or precision medicine in the foreseeable future.en_US
dc.description.sponsorshipThis work was supported by the National Science Foundation, Cellular & Biochemical Engineering Program under Grant No. 1805139. The authors would also like to acknowledge the Department of Chemical, Biochemical and Environmental Engineering at University of Maryland Baltimore County for funding support. Dr. Wan is supported by the funding from the Chinese Academy of Agricultural Sciences under grant number CAAS-ASTIP-2013-OCRI.en_US
dc.description.urihttps://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-019-1111-3en_US
dc.format.extent13 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m2t0jj-eegx
dc.identifier.citationXia Wan, Monireh Marsafari and Peng Xu, Engineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectives, Microbial Cell Factories ,2019, 18:61, https://doi.org/10.1186/s12934-019-1111-3en_US
dc.identifier.urihttps://doi.org/10.1186/s12934-019-1111-3
dc.identifier.urihttp://hdl.handle.net/11603/13418
dc.language.isoen_USen_US
dc.publisherBioMed Central Ltden_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Mechanical Engineering Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.relation.ispartofUMBC Student Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjecttranscriptional factorsen_US
dc.subjectsensorsen_US
dc.subjecteukaryotic cellsen_US
dc.subjectmetabolic engineeringen_US
dc.subjectintelligent biomanufacturingen_US
dc.subjectsynthetic biologyen_US
dc.titleEngineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectivesen_US
dc.typeTexten_US


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This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Except where otherwise noted, this item's license is described as This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.