Bio-Guided Isolation of Antimalarial Metabolites from the Coculture of Two Red Sea Sponge-Derived Actinokineospora and Rhodococcus spp.

Bio-Guided Isolation of Antimalarial Metabolites from the Coculture of Two Red Sea Sponge-Derived Actinokineospora and Rhodococcus spp.
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DOI:
10.3390/md19020109
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发表时间:
2021-02-12
期刊:
影响因子:
5.4
通讯作者:
Rateb ME
Rateb ME
中科院分区:
医学2区
文献类型:
--
作者:
Alhadrami HA;Thissera B;Hassan MHA;Behery FA;Ngwa CJ;Hassan HM;Pradel G;Abdelmohsen UR;Rateb ME

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共培养是一种生产技术,通过模仿自然栖息地的特征,主要是通过争夺食物和空间以及物种间的交流来激发微生物的生物合成能力。利用LC-HRMS代谢组学分析,对两种红海来源的放线菌,即放线菌素孢子菌(Actinokineospora spheciospongiae)菌株EG49和红球菌(Rhodococcus sp. UR59)进行混合培养,在其无菌培养物中诱导了几种不可见的代谢物。共培养发酵的抗疟诱导分离分离得到了在无菌条件下未见报道的安古霉素类放线素E(1)、H(2)、G(3)、四古洛尔(5)和蒽醌类毛细管甾酮B(6)。有趣的是,当信号分子n -乙酰-d-氨基葡萄糖(GluNAc)处理放线素孢子菌(Actinokineospora spheciospongiae菌株EG49)的无菌培养时,放线素孢素被诱导;这一发现证实了共培养在发现无菌发酵中尚未发现的微生物代谢物方面的有效性,其潜力可以与在发酵瓶中添加化学信号分子相媲美。分离得到的氨环素和蒽醌类化合物具有体外抗疟活性,且对赖氨酸- trna合成酶(PfKRS1)具有良好的抑制亲和力,具有开发新型抗疟结构基序的潜力。
Coculture is a productive technique to trigger microbes’ biosynthetic capacity by mimicking the natural habitats’ features principally by competition for food and space and interspecies cross-talks. Mixed cultivation of two Red Sea-derived actinobacteria, Actinokineospora spheciospongiae strain EG49 and Rhodococcus sp. UR59, resulted in the induction of several non-traced metabolites in their axenic cultures, which were detected using LC–HRMS metabolomics analysis. Antimalarial guided isolation of the cocultured fermentation led to the isolation of the angucyclines actinosporins E (1), H (2), G (3), tetragulol (5) and the anthraquinone capillasterquinone B (6), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the Actinokineospora spheciospongiae strain EG49 was treated with signalling molecule N-acetyl-d-glucosamine (GluNAc); this finding confirmed the effectiveness of coculture in the discovery of microbial metabolites yet to be discovered in the axenic fermentation with the potential that could be comparable to adding chemical signalling molecules in the fermentation flask. The isolated angucycline and anthraquinone compounds exhibited in vitro antimalarial activity and good biding affinity against lysyl-tRNA synthetase (PfKRS1), highlighting their potential developability as new antimalarial structural motif.
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