Study On Marine-derived Antibacterial Compound Curvulamine Fermentation Process

Curvulamine is an indolizidine alkaloid produced by the marine-derived fungus Curvularia sp. IFB-Z10. Previous literatures showed that, compared with clinical antimicrobial drug tinidazole, Curvulamine has better antibacterial activity against anaerobic pathogenic microorganisms, but the low yield in submerged fermentation has seriously limited its further researches. To solve this problem, this paper, mainly is to study the fermentation process of Curvulamine produced by marine-derived fungus Curvularia IFB-Z10.In this thesis, the optimal fermentation media and culture conditions for Curvulamine was carried out firstly. In the optimization process, we found that the fungal morphology was one of important factors affecting Curvulamine synthetic.Then, this work regulated the fungal morphology of Curvularia IFB-Z10 through adding microparticles and calcium ion aseptically. Finally, we established the related regulating strategy to form the plush-like small pellet of IFB-Z10 for enhancing the production.Moreover, on the base of morphology optimization, we further regulated the biosynthesis pathway by adding proline and alanine. Ultimately, the optimal fermentation process in shake flask was established and the Curvulamine production could reach 93.48 mg/L, which was about 11.58-fold of the initial production.To further improve the fermentation process of Curvulamine, the scale-up experiments was carried out based on the results in shake flask. In the scale-up process, it found that the fungal morphology and nitrogen deficiency were the key factors affecting Curvulamine synthesis. Through the optimization of seed culture series to control the fungal morphology and feeding yeast extract solution to supplement the nitrogen, Curvulamine production could reach 31.22 mg/L.