Secondary Metabolites Isolated from the Sponge-Associated Fungus Nigrospora oryzae
Secondary Metabolites Isolated from the Sponge-Associated Fungus Nigrospora oryzae
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从海绵相关真菌米黑孢中分离的次生代谢物
DOI：
10.1007/s10600-016-1837-7
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发表时间：
2016-09-01
影响因子：
0.8
通讯作者：
Xu, Shihai
中科院分区：
文献类型：
--
作者：
Ding, Lijian;Yuan, Wei;Xu, Shihai
海绵是海洋真菌多样性的顶级来源之一[1]。许多海绵相关真菌能够产生结构多样且具有高度生物活性的次级代谢产物[2]。此外，来自海绵相关真菌的代谢产物促进了制药，营养品和化妆品行业可持续产品的开发[3]。因此，我们一直关注海绵相关真菌的生物活性代谢产物。从中国南海永兴岛海域采集的海绵Clathrina luteoculcitella中分离到一种真菌Nigrospora luteoculcitella。黑孢霉产生大量代谢产物[4]。然而，目前还没有从海绵相关的黑孢菌中分离出次生代谢产物的研究。将该菌株在Czapek-Dox培养基中于室温下在人工海水中培养40天。将培养液用EtOAc萃取三次，并在真空下除去EtOAc溶剂，从10 L培养物中得到棕色胶状物（3.5 g）。将萃取物在硅胶色谱柱上进行色谱分离，并通过半制备型HPLC进一步纯化，得到化合物1（2 mg）、2（4 mg）、3（3 mg）、4（3 mg）、5（6 mg）、6（7 mg）和7（6 mg）。通过将NMR光谱数据与文献进行比较，这七种化合物被明确地鉴定为2，4-二氯苯甲酸（1）[5]、环-（Pro-Val）（2）[6]、环-（Pro-Leu）（3）[7]、环-（Pro-Ile）（4）[6]、环-（Pro-Tyr）（5）[6]、环-（Pro-Phe）（6）[8]和环-（Leu-Tyr）（7）[9]。2，4-二氯苯甲酸（1）和二酮哌嗪（DKPs）2-7均为首次从黑孢霉属中分离得到。DKP具有多种显著的生物活性，如抗微生物、抗氧化和抗肿瘤作用[10]。此外，革兰氏阴性细菌[11]和古细菌[12]通过激活或拮抗N-酰基高丝氨酸内酯介导的群体感应系统[11]利用DKP进行通信。结果表明，海绵源真菌黑孢霉产生的主要次生代谢产物为哌嗪二酮。事实上，DKP广泛存在于生命的三个领域，即细菌、古细菌和真核生物[10-12]。在这里，我们为DKP的广泛分布提供了一个可能的解释。作为种内通讯的群体感应信号，DKP在革兰氏阴性细菌[11]和古细菌[12]中以高转录水平合成。然而，在真菌中，DKP可能不参与真菌种内通讯[13]，但真菌分泌的生物活性DKP可能会给竞争对手带来错误信息，如微生物群落中的革兰氏阴性细菌或古细菌。最终，竞争者控制细胞密度，因此真菌在有限的资源下生存和生长。
Sponges represent one of the top-ranking sources of marine fungal diversity [1]. Many sponge-associated fungi are capable of producing structurally diverse and highly bioactive secondary metabolites [2]. Moreover, metabolites derived from sponge-associated fungi facilitate the development of sustainable products for the pharmaceutical, nutraceutical, and cosmetic industries [3]. Hence, we have paid ongoing attention to bioactive metabolites from sponge-associated fungi. The fungus Nigrospora oryzae was isolated from the marine sponge Clathrina luteoculcitella collected off Yongxing Island in the South China Sea. Nigrospora oryzae produces plenty of metabolites [4]. However, there is as yet no study on secondary metabolites isolated from the sponge-associated Nigrospora oryzae. The strain was cultured in Czapek–Dox medium at room temperature for 40 days in artificial seawater. The culture broth was extracted three times with EtOAc, and the EtOAc solvent was removed under vacuum to yield a brown gum (3.5 g) from a 10 L culture. The extract was chromatographed on a silica gel chromatographic column and further purified by semipreparative HPLC to afford compounds 1 (2 mg), 2 (4 mg), 3 (3 mg), 4 (3 mg), 5 (6 mg), 6 (7 mg), and 7 (6 mg). These seven compounds were unambiguously identified as 2, 4-dichlorobenzoic acid (1)[5], cyclo-(Pro-Val)(2)[6], cyclo-(Pro-Leu)(3)[7], cyclo-(Pro-Ile)(4)[6], cyclo-(Pro-Tyr)(5)[6], cyclo-(Pro-Phe)(6)[8], and cyclo-(Leu-Tyr)(7)[9] by comparing the NMR spectroscopic data with the literature.To the best of our knowledge, both 2, 4-dichlorobenzoic acid (1) and diketopiperazines (DKPs) 2–7 were isolated from the genus Nigrospora for the first time. DKPs exhibit diverse and remarkable biological activities, such as antimicrobial, antioxidant, and antitumor effects [10]. In addition, DKPs are utilized by gram-negative bacteria [11] and archaea [12] for communication by activating or antagonizing N-acylhomoserine lactone-mediated quorum sensing systems [11]. Our results showed that the main secondary metabolites produced by the sponge-derived fungus Nigrospora oryzae were diketopiperazines. Indeed, DKPs are widespread in three domains of life, ie, bacteria, archaea, and eukarya [10–12]. Here, we offer a possible explanation for the extensive distribution of DKPs. As quorum sensing signals for intraspecific communication, DKPs are synthesized at a high transcriptional level in gram-negative bacteria [11] and archaea [12]. Yet, in fungi, DKPs may not be involved in fungal intraspecific communication [13], but bioactive DKPs secreted by fungi could bring false information to competitors, like gram-negative bacteria or archaea in microbial communities. Ultimately, competitors control cell densities, and thus fungi survive and grow under limited resources.