title: Predictive combinatorial design of mRNA translation initiation regions for systematic optimization of gene expression levels.
abstract: Balancing the amounts of enzymes is one of the important factors to achieve optimum performance of a designed metabolic pathway. However, the random mutagenesis approach is impractical since it requires searching an unnecessarily large number of variants and often results in searching a narrow range of expression levels which are out of optimal level. Here, we developed a predictive combinatorial design method, called UTR Library Designer, which systematically searches a large combinatorial space of expression levels. It accomplishes this by designing synthetic translation initiation region of mRNAs in a predictive way based on a thermodynamic model and genetic algorithm. Using this approach, we successfully enhanced lysine and hydrogen production in Escherichia coli. Our method significantly reduced the number of variants to be explored for covering large combinatorial space and efficiently enhanced pathway efficiency, thereby facilitating future efforts in metabolic engineering and synthetic biology.
authors.affiliation: 1] Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784 [2].
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Seo
authors.affiliation: 1] School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784 [2].
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784.
authors.forename: Han-Saem
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784.
authors.forename: Jina
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784.
authors.forename: Seong Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784.
authors.forename: Jong Moon
authors.initials: JM
authors.lastname: Park
authors.affiliation: 1] Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784 [2] Division of IT Convergence Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784.
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.affiliation: 1] Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784 [2] School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, Korea, 790-784.
authors.forename: Gyoo Yeol
authors.initials: GY
authors.lastname: Jung
mesh_terms: D000465:Algorithms; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D015723:Gene Library; D060847:Metabolic Engineering / Q000379:methods; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D012333:RNA, Messenger