Today when the quest of new lead molecules to supply the development pipeline is driving the course of drug discovery, endophytic fungi with their outstanding biosynthetic potential seem to be highly promising avenues for natural product scientists. However, challenges such as the production of inadequate quantities of compounds, the attenuation or loss of ability of endophytes to produce the compound of interest when grown in culture and the inability of fungal endophytes to express their full biosynthetic potential in laboratory conditions have been the major constraints. These have led to the application of small chemical elicitors that induce epigenetic changes in fungi to activate their silent gene clusters optimizing the amount of metabolites of interest or inducing the synthesis of hitherto undescribed compounds. In this respect small molecular weight compounds which are known to function as inhibitors of histone deacetylase (HDAC), DNA methyltransferase (DNMT) and proteasome have proven their efficacy in enhancing or inducing the production of specialized metabolites by fungi. Moreover, organic solvents, metals and plants extracts are also acknowledged for their ability to cause shifts in fungal metabolism. We highlight the successful studies from the past two decades reporting the ability of structurally diverse small molecular weight compounds to elicit the production of previously undescribed metabolites from endophytic fungi grown in culture. This mini review argues in favor of chemical elicitation as an effective strategy to optimize the production of fungal metabolites and invigorate the pipeline of drug discovery with new chemical entities.

中文翻译：

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使用包括表观遗传修饰剂在内的小分子诱导物诱导内生真菌特化代谢物的最新进展

今天，当寻求新的先导分子来供应开发管道正在推动药物发现过程时，具有出色生物合成潜力的内生真菌似乎是天然产物科学家非常有前途的途径。然而，诸如生产数量不足的化合物、内生菌在培养中生长时产生目标化合物的能力减弱或丧失以及真菌内生菌无法在实验室条件下表达其全部生物合成潜力等挑战一直是主要的挑战。约束。这些导致了小化学诱导剂的应用，这些诱导剂诱导真菌的表观遗传变化，以激活它们的沉默基因簇，优化感兴趣的代谢物的数量或诱导迄今为止未描述的化合物的合成。在这方面，已知可作为组蛋白脱乙酰酶 (HDAC)、DNA 甲基转移酶 (DNMT) 和蛋白酶体抑制剂的小分子量化合物已证明它们在增强或诱导真菌产生特定代谢物方面的功效。此外，有机溶剂、金属和植物提取物也因其引起真菌代谢变化的能力而闻名。我们强调了过去二十年的成功研究，这些研究报告了结构多样化的小分子量化合物能够从培养中生长的内生真菌中引发以前未描述的代谢物的产生。这篇小型综述认为化学诱导是一种优化真菌代谢物生产和用新化学实体激活药物发现管道的有效策略。