Abstract：
:Escherichia coli gene expression knockdown using synthetic small RNA (sRNA) can be fine-tuned by altering sRNA sequences to modulate target mRNA-binding ability, but this requires thorough checking for off-target effects. Here, we present an sRNA gene expression knockdown system fine-tuned by using different promoters to modulate synthetic sRNA abundance. Our approach entails selecting knockdown target genes resulting from in silico flux response analysis and those related to product biosynthesis then screening strains transformed with a library of synthetic sRNA-promoter combinations for enhanced production. We engineered two E. coli strains, both utilizing fine-tuned repression of argF and glnA through our approach; one produced putrescine (42.3 ± 1.0 g/L) and the other L-proline (33.8 ± 1.6 g/L) by fed-batch culture. Fine-tuned gene knockdown by controlling sRNA abundance will be useful for rapid design of microbial strains through simultaneously optimizing expression of multiple genes at a systems level, as it overcomes the difficulties of constructing and testing many different sRNAs and checking their cross-reactivity.
journal_name
Cell Systjournal_title
Cell systemsauthors
Noh M,Yoo SM,Kim WJ,Lee SYdoi
10.1016/j.cels.2017.08.016subject
Has Abstractpub_date
2017-10-25 00:00:00pages
418-426.e4issue
4eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30388-5journal_volume
5pub_type
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