The guanacastepenes: A highly diverse family of secondary metabolites produced by an endophytic fungus
The guanacastepenes: A highly diverse family of secondary metabolites produced by an endophytic fungus
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DOI：
10.1021/ja016176y
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发表时间：
2001-10-10
影响因子：
15
通讯作者：
Clardy, J
中科院分区：
文献类型：
--
作者：
Brady, SF;Bondi, SM;Clardy, J
结构多样的“类天然产物”分子库构成了以小分子为基础的系统化方法理解生物过程的基础。结构多样的天然产物文库应该同样有用，几个小组正在研究组合生物合成方法来构建这样的文库。1作为最近对哥斯达黎加一种内生真菌调查的一部分，我们发现了一个结构多样化的二萜化合物家族，它为了解大自然如何构建天然产物库提供了一些洞察力。最初，我们对真菌CR115的天然产物感兴趣，因为其中至少有一种，鸟苷A(1)，2，3对金黄色葡萄球菌和粪肠球菌耐药菌株具有抗生素活性。2，4在研究过程中，CR115产生一系列相关但结构不同的代谢物变得明显起来。这些代谢物，如图1所示，由五个环系(图2)组成，装饰有各种官能团。许多代谢物中额外的互变异构和构象平衡提供了更大的结构多样性。同时进行了传统的形态学评估和核糖体DNA(RDNA)测序，试图对CR115进行特征分析。CR115在任何测试条件下都不产生孢子，也没有观察到其他支持其系统发育的形态特征。5用聚合酶链式反应扩增的内转录间隔区(ITS1和ITS2)和5.8 S rDNA基因的序列进行BLAST搜索，没有发现任何与CR115相同的序列。6最接近的序列是一种未鉴定的燕麦根担子菌，在ITS1、ITS2和5.8 S rDNA区域有90%的相似性。7这一rDNA序列数据，结合传统分类鉴定的失败，表明CR115可能代表了一种以前未描述的担子菌。
Libraries of structurally diverse “natural product-like” molecules form the basis for understanding biological processes in small molecule-based systematic approaches. Libraries of structurally diverse natural products should be equally useful, and several groups are working on combinatorial biosynthetic approaches to construct such libraries. 1 As part of a recent investigation of an endophytic fungus from Costa Rica, we discovered a remarkable family of structurally diverse diterpenes that provides some insight into how nature constructs libraries of natural products.Initially we were interested in the natural products of fungus CR115 because at least one of them, guanacastepene A (1), 2, 3 had antibiotic activity against drug resistant strains of Staphylococcus aureus and Enterococcus faecalis. 2, 4 During the course of that study it became clear that CR115 produces a family of related but structurally diverse metabolites. These metabolites, which are shown in Figure 1, comprise five ring systems (Figure 2) decorated with a variety of functional groups. Additional tautomeric and conformational equilibria in many of the metabolites give still greater structural diversity. Both a traditional morphological assessment and ribosomal DNA (rDNA) sequencing were performed in an attempt to characterize CR115. CR115 did not produce spores under any conditions tested, and no other morphological characteristics were observed that would suggest its phylogeny. 5 A BLAST search with the sequence derived from the polymerase chain reactionamplified internal transcribed spacers (ITS1 and ITS2) and the 5.8 S rDNA gene did not identify any sequences that were identical to CR115. 6 The most closely related sequence, an uncharacterized oat root Basidiomycete, shows 90% similarity over the ITS1, ITS2, and the 5.8 S rDNA regions. 7 This rDNA sequence data, in conjunction with the failure of traditional taxonomic identification, suggests that CR115 likely represents a previously undescribed Basidiomycete.