Modulating the direction of carbon flow in Escherichia coli to improve l-tryptophan production by inactivating the global regulator FruR.
The fructose repressor (FruR) affects carbon flux through the central metabolic pathways of Escherichia coli. In this study, l-tryptophan production in Escherichia coli FB-04 was improved by knocking out the fruR gene, thereby inactivating FruR. This fruR knockout strain, E. coli FB-04(ΔfruR), not only exhibited higher growth efficiency, it also showed substantially improved l-tryptophan production. l-tryptophan production by E. coli FB-04(ΔfruR) and l-tryptophan yield per glucose were increased by 62.5% and 52.4%, respectively, compared with the parent E. coli FB-04. Metabolomics analysis showed that the fruR knockout significantly enhances metabolic flow through glycolysis, the pentose phosphate pathway and the TCA cycle, increasing levels of critical precursors and substrates for l-tryptophan biosynthesis. These results indicate that fruR deletion should enhance l-tryptophan production and improve the efficiency of carbon source utilization independent of genetic background.
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China; School of Biotechnology and Key Laboratory of Industrial Biotechnology Ministry of Education, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China. Electronic address: nabestwishes@163.com.
Lina
L
Liu
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China; School of Biotechnology and Key Laboratory of Industrial Biotechnology Ministry of Education, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China. Electronic address: xgduan@jiangnan.edu.cn.
Xuguo
X
Duan
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China; School of Biotechnology and Key Laboratory of Industrial Biotechnology Ministry of Education, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China. Electronic address: jingwu@jiangnan.edu.cn.
Jing
J
Wu
D002244:Carbon / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics*; D055786:Gene Knockout Techniques; D060847:Metabolic Engineering; D055432:Metabolomics; D025341:Principal Component Analysis; D012097:Repressor Proteins / Q000235:genetics*; D014364:Tryptophan / Q000032:analysis / Q000378:metabolism*
D029968:Escherichia coli Proteins; C489416:FruR protein, E coli; D012097:Repressor Proteins; D002244:Carbon; D014364:Tryptophan
FruR; Global regulator; Metabolic flow; Metabolomics analysis; l-Tryptophan