Enhancing erythromycin precursor 6-dEB production by using synthetic small regulatory RNAs in Escherichia coli.
- Author:
Shujie SONG
;
Zhiqiang XIONG
;
Yong WANG
- Publication Type:Journal Article
- MeSH:
Down-Regulation;
Erythromycin;
biosynthesis;
Escherichia coli;
genetics;
metabolism;
Industrial Microbiology;
methods;
RNA
- From:
Chinese Journal of Biotechnology
2015;31(7):1039-1049
- CountryChina
- Language:Chinese
-
Abstract:
Although heterologous biosynthesis of polyketide erythromycin has been successfully achieved in Escherichia coli, the titer remains at a very low level (-10 mg/L). In this study, based on genome-scale metabolic model of E. coli, in silico method flux distribution comparison analysis was used to discover novel potential targets for heterologous 6-dEB biosynthesis. Synthetic small regulatory RNAs (sRNAs) was used to experimentally test 12 down-regulated targets. The results showed that repression of each of these target genes e.g. lsrC and ackA led to significantly improve heterologous 6-dEB biosynthesis. Using co-repression of lsrC and ackA, 6-dEB titer was improved by 59.9% in shake-flask with a maximum yield of 22.8 mg/L. This study indicates that combined flux distribution comparison analysis and synthetic small regulatory RNAs is an effective strategy to improve 6-dEB production in E. coli.
