Alhadrami Hani A, Thissera Bathini, Hassan Marwa H A, Behery Fathy A, Ngwa Che Julius, Hassan Hossam M, Pradel Gabriele, Abdelmohsen Usama Ramadan, Rateb Mostafa E
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. BOX 80402, Jeddah 21589, Saudi Arabia.
Molecular Diagnostic Laboratory, King Abdulaziz University Hospital, King Abdulaziz University, P.O. BOX 80402, Jeddah 21589, Saudi Arabia.
Mar Drugs. 2021 Feb 12;19(2):109. doi: 10.3390/md19020109.
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, strain EG49 and 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 (), H (), G (), tetragulol () and the anthraquinone capillasterquinone B (), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the strain EG49 was treated with signalling molecule -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.
共培养是一种有效的技术，主要通过模拟自然栖息地的特征，即通过争夺食物和空间以及种间相互作用来激发微生物的生物合成能力。对两种源自红海的放线菌菌株EG49和UR59进行混合培养，导致在其纯培养物中诱导产生了几种未追踪到的代谢产物，这些代谢产物通过液相色谱-高分辨质谱代谢组学分析进行检测。通过抗疟疾导向的共培养发酵分离，得到了角环素类放线菌素E（）、H（）、G（）、四氢呋喃醇（）和蒽醌类毛束草醌B（），这些在纯培养条件下均未被报道。有趣的是，之前当用信号分子N-乙酰-D-葡萄糖胺（GluNAc）处理菌株EG49的纯培养物时，诱导产生了放线菌素；这一发现证实了共培养在发现纯培养发酵中尚未发现的微生物代谢产物方面的有效性，其潜力可能与在发酵瓶中添加化学信号分子相当。分离得到的角环素和蒽醌化合物表现出体外抗疟疾活性以及对赖氨酰-tRNA合成酶（PfKRS1）良好的结合亲和力，突出了它们作为新型抗疟疾结构基序的潜在开发价值。
