文献类型：期刊文献

英文题名：Reconstruction of the Genome-Scale Metabolic Model of Saccharopolyspora erythraea and Its Application in the Overproduction of Erythromycin

作者：Xu, Feng[1];Lu, Ju[1];Ke, Xiang[1];Shao, Minghao[1];Huang, Mingzhi[1];Chu, Ju[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：12

期号：6

外文期刊名：METABOLITES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000816045300001)】；

基金：This work was financially supported by a grant from the National Key Research and Development Program of China (Grant NO. 2019YFA0904300), National Natural Science Foundation of China (Grant NO. 32071461), the National Key Research and Development Program of China (Grant NO. 2018YFA0900300).

语种：英文

外文关键词：genome-scale metabolic model; Saccharopolyspora erythraea; iJL1426; erythromycin production; n-propanol; process optimization

摘要：Saccharopolyspora erythraea is considered to be an effective host for erythromycin. However, little is known about the regulation in terms of its metabolism. To develop an accurate model-driven strategy for the efficient production of erythromycin, a genome-scale metabolic model (iJL1426) was reconstructed for the industrial strain. The final model included 1426 genes, 1858 reactions, and 1687 metabolites. The accurate rates of the growth predictions for the 27 carbon and 31 nitrogen sources available were 92.6% and 100%, respectively. Moreover, the simulation results were consistent with the physiological observation and C-13 metabolic flux analysis obtained from the experimental data. Furthermore, by comparing the single knockout targets with earlier published results, four genes coincided within the range of successful knockouts. Finally, iJL1426 was used to guide the optimal addition strategy of n-propanol during industrial erythromycin fermentation to demonstrate its ability. The experimental results showed that the highest erythromycin titer was 1442.8 mu g/mL at an n-propanol supplementation rate of 0.05 g/L/h, which was 45.0% higher than that without n-propanol supplementation, and the erythromycin-specific synthesis rate was also increased by 30.3%. Therefore, iJL1426 will lead to a better understanding of the metabolic capabilities and, thus, is helpful in a systematic metabolic engineering approach.