Coupling feedback genetic circuits with growth phenotype for dynamic population control and intelligent bioproduction

dc.contributor.authorLv, Yongkun
dc.contributor.authorQian, Shuai
dc.contributor.authorDu, Guocheng
dc.contributor.authorChen, Jian
dc.contributor.authorZhou, Jingwen
dc.contributor.authorXu, Peng
dc.date.accessioned2019-04-22T17:38:47Z
dc.date.available2019-04-22T17:38:47Z
dc.date.issued2019-03-30
dc.description.abstractMetabolic engineering entails target modification of cell metabolism to maximize cell's production potential. Due to the complexity of cell metabolism, feedback genetic circuits have emerged as basic tools to combat metabolic heterogeneity, enhance microbial cooperation as well as boost cell's productivity. This is generally achieved by applying social reward-punishment rules to eliminate cheaters and reward winners in a mixed cell population. With metabolite-responsive transcriptional factors to rewire gene expression, metabolic engineers are well-positioned to integrate feedback genetic circuits with growth fitness and achieve dynamic population control. Towards this goal, we argue that feedback genetic circuits and microbial interactions will be a golden mine for future metabolic engineering. We will summarize the design principles of engineering burden-driven feedback control to combat metabolic stress, implementing population quality control to eliminate cheater cell, applying product addiction to reward productive cell, as well as layering dual dynamic regulation to decouple cell growth from product formation. Collectively, these strategies will be useful to improve community-level cellular performance. Encoding such decision-marking functions and reprogramming cellular logics at population level will enable metabolic engineers to deliver robust cell factories and pave the way for intelligent bioproduction. We envision that various cellular regulation mechanisms and genetic/metabolic circuits could be exploited to achieve self-adaptive or autonomous metabolic function for diverse biotechnological and medical applications. Applying these design rules may offer us a genetic solution beyond bioprocess engineering strategies to further improve the cost-competitiveness of industrial fermentation.en_US
dc.description.sponsorshipThis work was supported by the Cellular & Biochem Engineering Program of the National Science Foundation 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. YL would like to thank the China Scholarship Council for funding support.en_US
dc.description.urihttps://www.sciencedirect.com/science/article/pii/S109671761930028Xen_US
dc.format.extent8 pagesen_US
dc.genrejournal articles postprintsen_US
dc.identifierdoi:10.13016/m2uuev-5gur
dc.identifier.citationYongkun Lv , Shuai Qian , Guocheng Du , Jian Chen , Jingwen Zhou , Peng Xu, Coupling feedback genetic circuits with growth phenotype for dynamic population control and intelligent bioproduction, Metabolic Engineering , Volume 54, July 2019, Pages 109-116, https://doi.org/10.1016/j.ymben.2019.03.009en_US
dc.identifier.urihttps://doi.org/10.1016/j.ymben.2019.03.009
dc.identifier.urihttp://hdl.handle.net/11603/13482
dc.language.isoen_USen_US
dc.publisherElsevier B.V.en_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemical, Biochemical & Environmental Engineering Department Collection
dc.relation.ispartofUMBC Faculty 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.rightsAccess to this item will begin on July 30, 2020.*
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectgenetic circuitsen_US
dc.subjectmetabolic engineeringen_US
dc.subjectdynamic population controlen_US
dc.subjectgrowth fitnessen_US
dc.subjectsynthetic biologyen_US
dc.titleCoupling feedback genetic circuits with growth phenotype for dynamic population control and intelligent bioproductionen_US
dc.typeTexten_US

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