Xu Feng, Lu Ju, Ke Xiang, Shao Minghao, Huang Mingzhi, Chu Ju
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, China.
Metabolites. 2022 Jun 1;12(6):509. doi: 10.3390/metabo12060509.
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 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 μg/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.
被认为是红霉素的有效宿主。然而，关于其代谢调控的了解却很少。为了开发一种准确的模型驱动策略以高效生产红霉素，为工业菌株重建了一个基因组规模的代谢模型（iJL1426）。最终模型包括1426个基因、1858个反应和1687个代谢物。对于可用的27种碳源和31种氮源，生长预测的准确率分别为92.6%和100%。此外，模拟结果与从实验数据获得的生理观察和碳代谢通量分析一致。此外，通过将单基因敲除靶点与早期发表的结果进行比较，在成功敲除范围内有四个基因相符。最后，iJL1426被用于指导工业红霉素发酵过程中正丙醇的最佳添加策略以展示其能力。实验结果表明，在正丙醇添加速率为0.05 g/L/h时，红霉素最高效价为1442.8 μg/mL，比不添加正丙醇时高45.0%，红霉素特异性合成速率也提高了30.3%。因此，iJL1426将有助于更好地理解代谢能力，从而有助于系统的代谢工程方法。
