Probing the Limits of Genetic Recoding in Essential Genes

被引：106

作者：

Lajoie, M. J. ^{[1
,2
]}

Kosuri, S. ^{[3
]}

Mosberg, J. A. ^{[1
,2
]}

Gregg, C. J. ^{[1
]}

Zhang, D. ^{[3
]}

Church, G. M. ^{[1
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Harvard Univ, Program Chem Biol, Cambridge, MA 02138 USA

[3] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA

来源：

SCIENCE | 2013年 / 342卷 / 6156期

关键词：

SYNONYMOUS CODON USAGE; ESCHERICHIA-COLI; IN-VIVO; TRANSLATION; GENOME; REVEALS; CELL; EXPRESSION; EFFICIENCY; SELECTION;

D O I：

10.1126/science.1241460

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Engineering radically altered genetic codes will allow for genomically recoded organisms that have expanded chemical capabilities and are isolated from nature. We have previously reassigned the translation function of the UAG stop codon; however, reassigning sense codons poses a greater challenge because such codons are more prevalent, and their usage regulates gene expression in ways that are difficult to predict. To assess the feasibility of radically altering the genetic code, we selected a panel of 42 highly expressed essential genes for modification. Across 80 Escherichia coli strains, we removed all instances of 13 rare codons from these genes and attempted to shuffle all remaining codons. Our results suggest that the genome-wide removal of 13 codons is feasible; however, several genome design constraints were apparent, underscoring the importance of a strategy that rapidly prototypes and tests many designs in small pieces.

引用

页码：361 / 363

页数：3

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