放线菌与枯草芽孢杆菌的共培养及其对活性次生代谢产物的影响

Coculture of actinomycetes with Bacillus subtilis and its effect on the bioactive secondary metabolites

摘要:

为探讨共培养对放线菌产生活性次生代谢产物的影响, 结合抗菌活性测定及HPLC-PDA分析, 研究了22株放线菌的单培养及其与枯草芽孢杆菌的共培养发酵代谢产物的差异, 并选取抗菌活性较强的链霉菌FXJ2.014进一步研究其代谢产物。发现FXJ2.014、FXJ1.296、AS 4.1252三株菌与枯草芽孢杆菌共培养时产生其在相同条件下单培养时没有的物质, 其中链霉菌FXJ2.014单培养时主要产生醌霉素A, 共培养时产物中增加了醌霉素结构类似物FXJ2.014-HB。进一步的抗菌、抗肿瘤活性测定结果表明, 两者的生物活性有较显著的差异, 且FXJ2.014-HB对多种肿瘤细胞系的抑制活性普遍弱于高毒性的醌霉素A, 为有潜力的细胞毒性较小的抗生素。共培养是一条很有希望的发掘放线菌活性次生代谢产物的新途径。

Abstract:

To explore the effect of coculturing actinomycetes with Bacillus subtilis on the production of bioactive secondary metabolites, we studied the difference between fermentation products of monocultures and the corresponding cocultures of 22 actinomycetes by antimicrobial assay and HPLC-PDA analysis. We selected Streptomyces strain FXJ2.014 with high bioactivity for further analysis and found additional metabolites in fermentation extracts of cocultures of strains FXJ2.014, FXJ1.296 and AS 4.1252 respectively with B. subtilis. Quinomycin A was the main bioactive metabolite produced by the monoculture of strain FXJ2.014, while a new quinomycin-like component named FXJ2.014-HB was produced when strain FXJ2.014 was cocultured with B. subtilis. Further tests of antimicrobial and antitumor activities indicated that FXJ2.014-HB and Quinomycin A had significant differences in terms of bioactivity. Moreover, the inhibitory activity of FXJ2.014-HB to a variety of tumor cell lines was weaker than the highly toxic Quinomycin A, indicating its potential to be an antibiotic with low cell toxicity. In conclusion, coculture can be used as a promising approach to discover bioactive secondary metabolites from actinomycetes.