Ke Xiang, Jiang Xing, Wang Shuohan, Tian Xiwei, Chu Ju
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
Qingdao Innovation Institute of East China University of Science and Technology, 596-1 East Jiushui Road, Qingdao, 266102, China.
Bioresour Bioprocess. 2024 Nov 1;11(1):105. doi: 10.1186/s40643-024-00817-w.
Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96-12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale.
与野生型NRRL 2338相比，比较转录组学揭示了高产突变菌株红色糖多孢菌HL3168 E3中与辅因子和维生素代谢相关的基因的不同表达模式。对九种维生素的作用进行了深入分析，确定焦磷酸硫胺素（TPP）、维生素B2、维生素B6、维生素B9、维生素B12和血红素是E3中红霉素生产的关键增强剂，可使红霉素效价提高7.96-12.66%。然后，应用Plackett-Burman设计和最速上升路径进一步优化维生素组合以实现最大生产效率，使摇瓶中的红霉素效价提高了39.2%。此外，靶向代谢组学和代谢通量分析阐明了维生素补充如何调节中心碳代谢，对三羧酸循环和蛋氨酸合成有显著影响，从而增加了红霉素合成所需的能量和前体的供应。这项工作突出了精确补充维生素以优化代谢途径从而提高红霉素产量的能力，并为工业规模应用提供了有价值的指导。
