氨基酸
谷氨酸棒杆菌
翻译(生物学)
终止密码子
大肠杆菌
生物
亮氨酸
基因
打开阅读框
丝氨酸
生产过剩
密码子使用偏好性
遗传学
生物化学
肽序列
基因组
信使核糖核酸
磷酸化
作者
Bo Zheng,Xiaoyan Ma,Ning Wang,Tingting Ding,Liwei Guo,Xiaorong Zhang,Yu Yang,Chun Li,Yi‐Xin Huo
标识
DOI:10.1038/s41467-018-05830-0
摘要
Abstract The translation of rare codons relies on their corresponding rare tRNAs, which could not be fully charged under amino acid starvation. Theoretically, disrupted or retarded translation caused by the lack of charged rare tRNAs can be partially restored by feeding or intracellular synthesis of the corresponding amino acids. Inspired by this assumption, we develop a screening or selection system for obtaining overproducers of a target amino acid by replacing its common codons with the corresponding synonymous rare alternative in the coding sequence of selected reporter proteins or antibiotic-resistant markers. Results show that integration of rare codons can inhibit gene translations in a frequency-dependent manner. As a proof-of-concept, Escherichia coli strains overproducing l -leucine, l -arginine or l -serine are successfully selected from random mutation libraries. The system is also applied to Corynebacterium glutamicum to screen out l -arginine overproducers. This strategy sheds new light on obtaining and understanding amino acid overproduction strains.
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