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Abstract：
Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1-A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1-A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. KEY POINTS: • Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. • Three polyketides and one asterriquinone were isolated from HDAC deleted strain. • Two different PKSs were reported in C. olivaceum SD-80A.
摘要：
丝状真菌中的组蛋白乙酰化修饰在表观遗传基因调控中起着至关重要的作用，并且与次级代谢产物（SM）生物合成基因簇（BGC）的转录密切相关。组蛋白脱乙酰酶（HDAC）在确定组蛋白乙酰化修饰的程度中起关键作用，并充当靶BGC表达活性的触发因素。Chaetomium属被广泛认为是新型和生物活性SMs的丰富来源。橄榄ChaetomiumSD-80A的I类HDAC基因的缺失，g7489对SMBGC的表达诱导实质性的多效性作用。橄榄梭菌SD-80A÷g7489菌株在形态上表现出显著变化，孢子形成能力，和次级代谢概况，导致新的复合峰的出现。值得注意的是,从该突变菌株中分离出三个聚酮化合物（A1-A3）和一个星三醌（A4）。此外，我们的研究探索了A1-A4的BGC，证实了两种聚酮合酶（PKSs）的功能。总的来说，我们的发现强调了分子表观遗传学方法在Chaetomium物种中阐明新型活性化合物及其生物合成元素的潜在潜力。这一发现对毛虫资源的勘探和利用具有重要意义。关键点:•I类组蛋白脱乙酰酶激活的次级代谢物基因簇的缺失。•从HDAC缺失菌株中分离出三种聚酮化合物和一种星三醌。·在橄榄梭菌SD-80A中报告了两种不同的PKS。
