Abstract

In pursuit of discovering novel compounds of pharmacological significance, plants and microbes are the potential sources. Endophytic fungi are well-known producers of a myriad class of bioactive metabolites but in laboratory conditions, a substantial number of biosynthetic pathways remain quiescent or under-expressed in conventional culture conditions. Hence, major potential of them is neglected during regular fermentation process. Epigenetic modifiers are reported to modulate fungal genome by altering the expression of metabolite production. Our present study evidences the induction of cryptic secondary metabolite production by Hypoxylon anthochroum, a foliar endophytic fungus of Carica papaya when treated with extracts of garlic and curry leaves. Garlic (Allium sativum), produces allyl mercaptan and diallyl disulfide as the major constituents of organosulfur compounds, which are known to act as inhibitors of histone deacetylases (HDAC). Similarly, Curry leaves (Murraya koenigii) produce mahanine, a carbazole alkaloid, causes DNA methyltransferase (DNMT) inhibition. Hypoxylon anthochroum, when treated with extract of garlic and curry leaves, resulted in 416.12 and 333.33% increase in yield of secondary metabolites, 89% and 85% increase in antioxidant property respectively, along with enhanced antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. High-performance liquid chromatography analysis of the crude extract of H. anthochroum revealed the induction of 19 and 10 new compounds when treated with garlic and curry leaf extracts, respectively, when compared to untreated control. This study suggests that treatment with HDAC inhibitor in the form of garlic extract was more effective than treatment with DNMT inhibitor in curry leaf extract in inducing cryptic metabolites.

Graphic Abstract

中文翻译：

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天然存在的表观遗传修饰因子刺激次生火成虫次级代谢产物的产生

摘要

为了发现具有药理学意义的新型化合物，植物和微生物是潜在的来源。内生真菌是无数类生物活性代谢物的众所周知的生产者，但在实验室条件下，许多生物合成途径在常规培养条件下仍保持静止或表达不足。因此，在常规发酵过程中它们的主要潜力被忽略了。据报道表观遗传修饰剂通过改变代谢产物的表达来调节真菌基因组。我们的研究表明，用大蒜和咖喱叶提取物处理后，番木瓜的叶内生真菌Hypoxylon anthochroum诱导了隐性次级代谢产物的产生。大蒜（大蒜）），产生烯丙基硫醇和二烯丙基二硫化物，作为有机硫化合物的主要成分，已知它们可作为组蛋白脱乙酰基酶（HDAC）的抑制剂。同样，咖喱叶（Murraya koenigii）产生的甘氨酸是咔唑生物碱，可引起DNA甲基转移酶（DNMT）抑制。用大蒜和咖喱叶提取物处理的次生火炭菌可使次生代谢产物的收率分别提高416.12和333.33％，抗氧化性分别提高89％和85％，同时对枯草芽孢杆菌，金黄色葡萄球菌，大肠埃希氏菌的抗菌活性增强。大肠杆菌和铜绿假单胞菌。炭疽菌粗提物的高效液相色谱分析表明，与未处理的对照相比，分别用大蒜和咖喱叶提取物处理时，诱导了19种和10种新化合物的诱导。这项研究表明，在咖喱叶提取物中，以大蒜提取物形式使用HDAC抑制剂治疗比用DNMT抑制剂治疗更有效。

图形摘要