Unlocking the metabolic potential of endophytic fungi through epigenetics: a paradigm shift for natural product discovery and plant-microbe interactions.

IF 10.6 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rui Liu, Xiao-Ping Peng, David J Newman, Diane Purchase, Gang Li, Souvik Kusari
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Abstract

Covering: up to December 2024Microbial metabolic pathways, including those of endophytic fungi, offer significant potential for synthesizing secondary metabolites, regardless of their ecological niche. These pathways can be modulated at the molecular level through genome and epigenome manipulation. The metabolic activation of fungal endophytes using epigenetics presents an exciting frontier in science, paving the way for advanced biotechnological applications and enhancing our understanding of these microorganisms' roles in ecosystems. This review examines the significant role of epigenetics in the biosynthesis of secondary metabolites from fungal endophytes, which is vital for drug discovery. Our primary focus centers on studies that explore the epigenetic modulation of endophytic fungi up until December 2024. Acknowledging the rapidly evolving landscape of epigenetic research in this field, which has limited examples for endophytic fungi, we provide crucial foundational insights into fungal epigenetics and relate these insights to the broader context of plant-microbe interactions and endophytic fungal epigenetics, supported by relevant examples. Key mechanisms, such as histone acetylation, histone methylation, and DNA methylation, are discussed alongside recent advances in small-molecule epigenetic modulators that can activate silent biosynthetic gene clusters (BGCs). Further, chromatin-dependent regulation of these BGCs and methods for probing chromatin modifications and secondary metabolism in fungi are discussed. The role of CRISPR-Cas9 genome editing, combined with epigenetic strategies, is highlighted, showcasing its ability to alter the metabolite profiles of fungal endophytes. Finally, we explore how artificial intelligence (AI), machine learning (ML), and deep learning (DL) innovations are transforming research in chemical epigenomics at the plant-microbe interface.

通过表观遗传学解锁内生真菌的代谢潜力:天然产物发现和植物-微生物相互作用的范式转变。
微生物代谢途径,包括内生真菌的代谢途径,无论其生态位如何,都具有合成次生代谢物的巨大潜力。这些途径可以通过基因组和表观基因组操作在分子水平上进行调节。利用表观遗传学研究真菌内生菌的代谢激活是一个令人兴奋的科学前沿,为先进的生物技术应用铺平了道路,并增强了我们对这些微生物在生态系统中的作用的理解。本文综述了表观遗传学在真菌内生菌次生代谢物的生物合成中的重要作用,这对药物发现至关重要。我们的主要重点是研究内生真菌的表观遗传调节,直到2024年12月。认识到该领域表观遗传学研究的快速发展,内生真菌的例子有限,我们提供了真菌表观遗传学的关键基础见解,并将这些见解与植物-微生物相互作用和内生真菌表观遗传学的更广泛背景联系起来,并得到相关实例的支持。关键机制,如组蛋白乙酰化,组蛋白甲基化和DNA甲基化,讨论了小分子表观遗传调节剂的最新进展,可以激活沉默的生物合成基因簇(BGCs)。此外,还讨论了这些bgc的染色质依赖性调控以及探测真菌中染色质修饰和次生代谢的方法。强调了CRISPR-Cas9基因组编辑与表观遗传策略相结合的作用,展示了其改变真菌内生菌代谢物谱的能力。最后,我们探讨了人工智能(AI)、机器学习(ML)和深度学习(DL)创新如何在植物-微生物界面上改变化学表观基因组学的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Natural Product Reports
Natural Product Reports 化学-生化与分子生物学
CiteScore
21.20
自引率
3.40%
发文量
127
审稿时长
1.7 months
期刊介绍: Natural Product Reports (NPR) serves as a pivotal critical review journal propelling advancements in all facets of natural products research, encompassing isolation, structural and stereochemical determination, biosynthesis, biological activity, and synthesis. With a broad scope, NPR extends its influence into the wider bioinorganic, bioorganic, and chemical biology communities. Covering areas such as enzymology, nucleic acids, genetics, chemical ecology, carbohydrates, primary and secondary metabolism, and analytical techniques, the journal provides insightful articles focusing on key developments shaping the field, rather than offering exhaustive overviews of all results. NPR encourages authors to infuse their perspectives on developments, trends, and future directions, fostering a dynamic exchange of ideas within the natural products research community.
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