González-Menéndez Victor, Crespo Gloria, Toro Clara, Martín Jesús, de Pedro Nuria, Tormo Jose R, Genilloud Olga
Fundación MEDINA, Parque Tecnológico Ciencias de la Salud. Avda. del Conocimiento 34, 18016 Granada, Spain.
Metabolites. 2019 Sep 21;9(10):197. doi: 10.3390/metabo9100197.
Fungi are one of the most prolific sources of microbial secondary metabolites. The production of new metabolites can be achieved using multiple fermentation conditions and by adding small-molecule effectors, including epigenetic modifiers. In the framework of our Natural Product screening programme targeting the discovery of new antimicrobial compounds, we applied multiple fermentation conditions and adsorptive polymeric resins on a large collection of fungal endophytes, to increase and stimulate their fungal secondary metabolite production. During this work the endophytic fungus CF-090383 showed antimicrobial activity only when grown in presence of adsorptive polymeric resins. In addition, seven epigenetic modifiers were added to fermentations of this endophytic fungus, in an attempt to activate its cryptic pathways as well as to analyse the metabolites produced under these conditions. was seen to produce three different mycotoxin dendrodolides when the epigenetic modifiers 5-azacytidine and valproic acid were added to the fermentations, and these compounds were further characterized. However, the fungus produced the fatty acid synthesis inhibitor cerulenin, a molecule not previously described to be produced by this fungal species, only when cultivated in presence of the XAD-16 resin. We have found that the addition of XAD-16 resin resulted in four-fold higher titers in the production of cerulenin when compared to the best production conditions described in literature for the original fungal producer strain, , in a zeolite-based fermentation, used as an ammonium ion-trapping agent. The production of cerulenin by this strain of , represents an alternative source for the improved production of cerulenin with better yields.
真菌是微生物次级代谢产物最多产的来源之一。利用多种发酵条件并添加小分子效应物(包括表观遗传修饰剂)可以实现新代谢产物的产生。在我们旨在发现新型抗菌化合物的天然产物筛选计划框架内,我们对大量真菌内生菌应用了多种发酵条件和吸附性聚合物树脂,以增加并刺激它们产生真菌次级代谢产物。在这项工作中,内生真菌CF - 090383仅在吸附性聚合物树脂存在的情况下生长时才表现出抗菌活性。此外,向这种内生真菌的发酵过程中添加了七种表观遗传修饰剂,试图激活其隐秘途径并分析在这些条件下产生的代谢产物。当向发酵过程中添加表观遗传修饰剂5 - 氮杂胞苷和丙戊酸时,发现该真菌产生了三种不同的霉菌毒素树状多醇,并且对这些化合物进行了进一步表征。然而,该真菌仅在XAD - 16树脂存在的情况下培养时才产生脂肪酸合成抑制剂浅蓝菌素,这是一种此前未描述由该真菌物种产生的分子。我们发现,与文献中描述的原始真菌生产菌株在基于沸石的发酵中用作铵离子捕获剂时的最佳生产条件相比,添加XAD - 16树脂使浅蓝菌素的产量提高了四倍。该菌株产生浅蓝菌素,为提高浅蓝菌素产量提供了另一种更好的来源。