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表观遗传修饰剂作为真菌中生物活性次生代谢物的诱导剂。

Epigenetic modifiers as inducer of bioactive secondary metabolites in fungi.

机构信息

Fermentation & Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

Biotechnol Lett. 2024 Jun;46(3):297-314. doi: 10.1007/s10529-024-03478-z. Epub 2024 Apr 12.

Abstract

Scientists are making efforts to search for new metabolites as they are essential lead molecules for the drug discovery, much required due to the evolution of multi drug resistance and new diseases. Moreover, higher production of known drugs is required because of the ever growing population. Microorganisms offer a vast collection of chemically distinct compounds that exhibit various biological functions. They play a crucial role in safeguarding crops, agriculture, and combating several infectious ailments and cancer. Research on fungi have grabbed a lot of attention after the discovery of penicillin, most of the compounds produced by fungi under normal cultivation conditions are discovered and now rarely new compounds are discovered. Treatment of fungi with the epigenetic modifiers has been becoming very popular since the last few years to boost the discovery of new molecules and enhance the production of already known molecules. Epigenetic literally means above genetics that actually does not alter the genome but alter its expression by altering the state of chromatin from heterochromatin to euchromatin. Chromatin in heterochromatin state usually doesn't express because it is closely packed by histones in this state. Epigenetic modifiers loosen the packing of chromatin by inhibiting DNA methylation and histone deacetylation and thus permit the expression of genes that usually remain dormant. This study delves into the possibility of utilizing epigenetic modifying agents to generate pharmacologically significant secondary metabolites from fungi.

摘要

科学家们正在努力寻找新的代谢物,因为它们是药物发现的重要先导分子,由于多药耐药性和新疾病的出现,这些先导分子的需求非常大。此外,由于人口不断增长,对已知药物的更高产量的需求也在不断增加。微生物提供了大量具有不同化学结构的化合物,这些化合物具有各种生物功能。它们在保护作物、农业以及对抗多种传染病和癌症方面发挥着至关重要的作用。在发现青霉素后,对真菌的研究引起了广泛关注,现在已经发现了大部分在正常培养条件下由真菌产生的化合物,很少有新的化合物被发现。近年来,用表观遗传修饰剂治疗真菌已变得非常流行,这是为了促进新分子的发现并提高已有分子的产量。表观遗传字面意思是遗传学之上的,它实际上不会改变基因组,而是通过改变染色质的状态从异染色质变为常染色质来改变其表达。在这种状态下,染色质紧密包装,因此异染色质状态下的染色质通常不会表达。表观遗传修饰剂通过抑制 DNA 甲基化和组蛋白去乙酰化来松开染色质的包装,从而允许通常处于休眠状态的基因表达。本研究探讨了利用表观遗传修饰剂从真菌中产生具有药理意义的次生代谢物的可能性。

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