RESUMO
Swainsonine (SW) is a substance with both animal neurotoxicity and natural anticancer activity produced by the metabolism of endophytic fungus Alternaria section Undifilum oxytropis of locoweed. This paper produced SW by fermentation of the endophytic fungus A. oxytropis of locoweed and obtained the optimal ultrasonic-assisted extraction process of SW by the response surface methodology. Meanwhile, four mutant strains with significant and stable SW-producing properties were screened out after the mutagenesis of A. oxytropis by heavy-ion irradiation. Of these, three were high-yielding stains and one was a low-yielding strain. In addition, through the analysis of metabolomics studies, it was speculated that the different SW production performance of the mutant might be related to the biosynthesis and utilization of L-lysine, L-2-aminoadipate-6-semialdehyde, etc. These results laid the foundation for the expansion of SW production, artificial construction of low-toxic locoweed and clarification of the SW biosynthesis pathway in A. oxytropis.
RESUMO
Swainsonine, an indolizidine alkaloid, is a promising anti-tumorigenic compound. Biological production of swainsonine was prospective, but the low swainsonine yield of wild type Alternaria oxytropis limited its production on a large scale. In present work, a stable A. oxytropis mutant UO1 with swanisonine yield of 14.84% higher than the wild-type strain was successfully obtained after heavy-ion irradiation. The A. oxytropis mutant UO1 and original wild-type strain were futher evaluated for SW concentrations under different factors. Results showed that the optimum culture temperature was 25°C. The optimum initial medium pH was 6.5 and the optimum inoculum size was 2 mL per 200 mL. Addition of the biosynthetic precursor L-pipecolic acids and L-lysine appropriately could increase the SW synthesis. These findings provided a theoretical basis and scientific data for the industrial production of swainsonine.