Natural products derived from microorganisms play a key role in the discovery and development of drug candidates. Several drugs have originated from secondary metabolites or their derivatives from microorganisms in clinical therapy, such as penicillin, cyclosporine, and lovastatin. Application of epigenetic methodology on modulation and stimulation of secondary metabolites from fungi provides a practical way to investigate fungal natural products. Addition of enzyme inhibitors such as histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors to activate silent biosynthetic gene clusters result in the potential for generating a variety of secondary metabolites with novel skeletons and diversity of stereochemistry, as well as unprecedented heterocyclic rings. After triggering the epigenetic modifiers, some species were affected and produced several uncovered secondary metabolites. Although this strategy has been successfully carried out for few reports, the results of this research field have demonstrated high potential for engineering the secondary metabolites from fungi. By utilizing the above strategy, modulation and characterization of the secondary metabolites from fungi make them able to generate several novel or bioactive natural products that will provide sources for discovering new candidates. Furthermore, the epigenetic modulation technique integrated with pharmacological assays for further investigation becomes a promising avenue for improvement of natural products research and development. This review summarizes the progression and development of epigenetic manipulation in fungal natural product research.

源自微生物的天然产物在候选药物的发现和开发中起关键作用。在临床治疗中，几种药物源自次级代谢产物或它们的衍生自微生物，例如青霉素，环孢霉素和洛伐他汀。表观遗传学方法在调节和刺激真菌次级代谢产物中的应用为研究真菌天然产物提供了一种实用的方法。添加酶抑制剂（例如组蛋白脱乙酰基酶（HDAC）或DNA甲基转移酶（DNMT）抑制剂）以激活沉默的生物合成基因簇导致产生具有新颖骨架和立体化学多样性以及前所未有的杂环的各种次级代谢产物的潜力。触发表观遗传修饰符后，一些物种受到影响并产生了几种未发现的次级代谢产物。尽管很少有报道成功地实施了该策略，但是该研究领域的结果显示出了对真菌次级代谢产物进行工程改造的巨大潜力。通过利用上述策略，真菌的次级代谢产物的调节和表征使它们能够产生几种新颖的或具有生物活性的天然产物，这将为发现新的候选物提供来源。此外，将表观遗传调控技术与药理学分析相结合以进一步研究，成为改善天然产物研发的有前途的途径。这篇综述总结了真菌天然产物研究中表观遗传操纵的进展和发展。