Molecular dynamics simulation and validation of spiramycin extraction using the thermosensitive polymer NPE-108/water aqueous two-phase system

Spiramycin is a 16-membered macrolide antibiotic widely used in the medical field. Industrial extraction of antibiotics from fermentation broth using organic solvents raises various environmental and health concerns. In this study, a thermosensitive polymer, NPE-108, was used to construct an aqueous two-phase system (ATPS) for the extraction of spiramycin. We used Gromacs software to develop a molecular dynamics simulation model to reveal the distribution mechanism of spiramycin molecules in the NPE-108/water ATPS from a microscopic perspective. Additionally, we examined the effects of volume ratio, temperature, and pH on extraction through experimentation. Under the optimal conditions for forward extraction, the distribution coefficient and extraction efficiency were 25.3 and 89.9%, respectively. Under the optimal conditions for back extraction, the distribution coefficient and extraction efficiency were 6.8 and 81.5%, respectively. Optimization of crystallization conditions resulted in a crystal yield of 88.1% and a purity of 98.4%. The content of both spiramycin components and impurities in the crystalline sample met the requirements of the European Pharmacopeia. The results of this study provided insights into molecular interactions and the extraction process, offering a more environmentally friendly and economically viable alternative for industrial spiramycin production.