Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China.
School of Life and Health Sciences, Hainan University, Haikou 570228, China.
Mar Drugs. 2024 Jul 24;22(8):332. doi: 10.3390/md22080332.
Co-cultivation is a powerful emerging tool for awakening biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. It has recently been used increasingly extensively to study natural interactions and discover new bioactive metabolites. As a part of our project aiming at the discovery of structurally novel and biologically active natural products from mangrove endophytic fungi, an established co-culture of a strain of DHS-48 with another genus fungus DHS-11, both endophytes in mangrove , proved to be very efficient to induce the production of new metabolites as well as to increase the yields of respective target metabolites. A detailed chemical investigation of the minor metabolites produced by the co-culture of these two titled fungal strains led to the isolation of six alkaloids (-), two sterols (, ), and six polyketides (-). In addition, all the compounds except and , as well as three new metabolites phomopyrazine (), phomosterol C (), and phomopyrone E (), were not present in discrete fungal cultures and only detected in the co-cultures. The structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assumed by electronic circular dichroism (ECD) calculations. Subsequently, the cytotoxic, immunosuppressive, and acetylcholinesterase inhibitory properties of all the isolated metabolites were determined in vitro. Compound exhibited moderate inhibitory activity against ConA-induced T and LPS-induced B murine splenic lymphocytes, with IC values of 35.75 ± 1.09 and 47.65 ± 1.21 µM, respectively.
共培养是一种强大的新兴工具，可用于唤醒在人工培养条件下转录沉默的生物合成基因簇（BGCs）。它最近越来越多地被用于研究自然相互作用和发现新的生物活性代谢物。作为我们从红树林内生真菌中发现结构新颖和具有生物活性天然产物的项目的一部分，一株 DHS-48 菌株与另一株 DHS-11 真菌（均为红树林内生真菌）的共培养被证明非常有效地诱导新代谢物的产生，并提高各自目标代谢物的产量。对这两种真菌菌株共培养产生的少量代谢物的详细化学研究导致分离出六种生物碱（-）、两种甾醇（、）和六种聚酮化合物（-）。此外，除了和 ，以及三种新代谢物（phomopyrazine()、phomosterol C()和 phomopyrone E()）外，所有化合物都不存在于离散真菌培养物中，仅在共培养物中检测到。结构根据光谱分析阐明，绝对构型通过电子圆二色性（ECD）计算假设。随后，在体外测定了所有分离代谢物的细胞毒性、免疫抑制和乙酰胆碱酯酶抑制特性。化合物 对 ConA 诱导的 T 和 LPS 诱导的 B 小鼠脾淋巴细胞显示出中等抑制活性，IC 值分别为 35.75 ± 1.09 和 47.65 ± 1.21 µM。
