Zhou Xiaojie, Zhang Xiaoxiao, Wang Dan, Luo Ruoshi, Qin Zhao, Lin Fanzhen, Xia Xue, Liu Xuemei, Hu Ge
Department of Chemical Engineering, School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, P. R. China.
AgroParisTech, 22 place de l'Agronomie, 91120 Palaiseau, France.
ACS Omega. 2024 May 10;9(20):22386-22397. doi: 10.1021/acsomega.4c02060. eCollection 2024 May 21.
Salidroside, a valuable phenylethanoid glycoside, is obtained from plants belonging to the genus, known for its diverse biological properties. At present, salidroside is still far from large-scale industrial production due to its lower titer and higher process cost. In this study, we have for the first time increased salidroside production by enhancing UDP-glucose supply . We constructed an UDP-glucose regeneration system that works in conjunction with UDP-glucose transferase from innovatively to improve UDP-glucose availability. And a coculture was formed in order to enable salidroside synthesis. Confronted with the influence of tyrosol on strain growth, an adaptive laboratory evolution strategy was implemented to enhance the strain's tolerance. Similarly, salidroside production was optimized through refinement of the fermentation medium, the inoculation ratio of the two microbes, and the inoculation size. The final salidroside titer reached 3.8 g/L. This was the highest titer achieved at the shake flask level in the existing reports. And this marked the first successful synthesis of salidroside in an enhanced UDP-glucose system using sucrose. The cost was reduced by 93% due to the use of inexpensive substrates. This accomplishment laid a robust foundation for further investigations into the synthesis of other notable glycosides and natural compounds.
红景天苷是一种珍贵的苯乙醇苷，从该属植物中提取，以其多样的生物学特性而闻名。目前，由于红景天苷的产量较低且生产成本较高，距离大规模工业化生产仍有很大差距。在本研究中，我们首次通过增强UDP-葡萄糖供应来提高红景天苷的产量。我们创新性地构建了一个与UDP-葡萄糖转移酶协同工作的UDP-葡萄糖再生系统，以提高UDP-葡萄糖的可用性。并形成了共培养体系以实现红景天苷的合成。面对酪醇对菌株生长的影响，实施了适应性实验室进化策略以提高菌株的耐受性。同样，通过优化发酵培养基、两种微生物的接种比例和接种量来优化红景天苷的生产。最终红景天苷产量达到3.8 g/L。这是现有报道中摇瓶水平下达到的最高产量。这标志着首次在使用蔗糖的增强型UDP-葡萄糖系统中成功合成红景天苷。由于使用了廉价底物，成本降低了93%。这一成果为进一步研究其他重要糖苷和天然化合物的合成奠定了坚实基础。
