{"title":"An Update of Fungal Endophyte Diversity and Strategies for Augmenting Therapeutic Potential of their Potent Metabolites: Recent Advancement","authors":"Chandrabhan Prajapati, Sachchida Nand Rai, Anurag Kumar Singh, Balu A. Chopade, Yashveer Singh, Santosh Kumar Singh, Shafiul Haque, Miguel Angel Prieto, Ghulam Md Ashraf","doi":"10.1007/s12010-024-05098-9","DOIUrl":null,"url":null,"abstract":"<div><p>Endophytic fungi represent a significant renewable resource for the discovery of pharmaceutically important compounds, offering substantial potential for new drug development. Their ability to address the growing issue of drug resistance has drawn attention from researchers seeking novel, nature-derived lead molecules that can be produced on a large scale to meet global demand. Recent advancements in genomics, metabolomics, bioinformatics, and improved cultivation techniques have significantly aided the identification and characterization of fungal endophytes and their metabolites. Current estimates suggest there are approximately 1.20 million fungal endophytes globally, yet only around 16% (190,000) have been identified and studied in detail. This underscores the vast untapped potential of fungal endophytes in pharmaceutical research. Research has increasingly focused on the transformation of bioactive compounds by fungal endophytes through chemical and enzymatic processes. A notable example is the anthraquinone derivative 6-O-methylalaternin, whose cytotoxic potential is enhanced by the addition of a hydroxyl group, sharing structural similarities with its parent compound macrosporin. These structure-bioactivity studies open up new avenues for developing safer and more effective therapeutic agents by synthesizing targeted derivatives. Despite the immense promise, challenges remain, particularly in the large-scale cultivation of fungal endophytes and in understanding the complexities of their biosynthetic pathways. Additionally, the genetic manipulation of endophytes for optimized metabolite production is still in its infancy. Future research should aim to overcome these limitations by focusing on more efficient cultivation methods and deeper exploration of fungal endophytes’ genetic and metabolic capabilities to fully harness their therapeutic potential.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"197 5","pages":"2799 - 2866"},"PeriodicalIF":3.3000,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12010-024-05098-9.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Applied Biochemistry and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://link.springer.com/article/10.1007/s12010-024-05098-9","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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Abstract
Endophytic fungi represent a significant renewable resource for the discovery of pharmaceutically important compounds, offering substantial potential for new drug development. Their ability to address the growing issue of drug resistance has drawn attention from researchers seeking novel, nature-derived lead molecules that can be produced on a large scale to meet global demand. Recent advancements in genomics, metabolomics, bioinformatics, and improved cultivation techniques have significantly aided the identification and characterization of fungal endophytes and their metabolites. Current estimates suggest there are approximately 1.20 million fungal endophytes globally, yet only around 16% (190,000) have been identified and studied in detail. This underscores the vast untapped potential of fungal endophytes in pharmaceutical research. Research has increasingly focused on the transformation of bioactive compounds by fungal endophytes through chemical and enzymatic processes. A notable example is the anthraquinone derivative 6-O-methylalaternin, whose cytotoxic potential is enhanced by the addition of a hydroxyl group, sharing structural similarities with its parent compound macrosporin. These structure-bioactivity studies open up new avenues for developing safer and more effective therapeutic agents by synthesizing targeted derivatives. Despite the immense promise, challenges remain, particularly in the large-scale cultivation of fungal endophytes and in understanding the complexities of their biosynthetic pathways. Additionally, the genetic manipulation of endophytes for optimized metabolite production is still in its infancy. Future research should aim to overcome these limitations by focusing on more efficient cultivation methods and deeper exploration of fungal endophytes’ genetic and metabolic capabilities to fully harness their therapeutic potential.
内生真菌是发现重要药物化合物的重要再生资源，为新药开发提供了巨大的潜力。它们解决日益严重的耐药性问题的能力引起了研究人员的注意，这些研究人员正在寻找新的、自然衍生的铅分子，可以大规模生产以满足全球需求。基因组学、代谢组学、生物信息学和改进的培养技术的最新进展极大地帮助了真菌内生菌及其代谢物的鉴定和表征。目前的估计表明，全球大约有120万真菌内生菌，但只有约16%（19万）被确定和详细研究。这强调了真菌内生菌在药物研究中的巨大潜力。研究越来越关注真菌内生菌通过化学和酶的过程转化生物活性化合物。一个显著的例子是蒽醌衍生物6- o -甲基丙环菌素，其细胞毒性潜力通过添加羟基而增强，与其母体化合物大孢素具有结构相似性。这些结构-生物活性研究为通过合成靶向衍生物开发更安全、更有效的治疗药物开辟了新的途径。尽管前景广阔，但挑战依然存在，特别是在真菌内生菌的大规模培养和了解其生物合成途径的复杂性方面。此外，内生菌的遗传操作优化代谢物的生产仍处于起步阶段。未来的研究应着眼于克服这些局限性，关注更有效的培养方法，深入探索真菌内生菌的遗传和代谢能力，以充分利用其治疗潜力。
期刊介绍：
This journal is devoted to publishing the highest quality innovative papers in the fields of biochemistry and biotechnology. The typical focus of the journal is to report applications of novel scientific and technological breakthroughs, as well as technological subjects that are still in the proof-of-concept stage. Applied Biochemistry and Biotechnology provides a forum for case studies and practical concepts of biotechnology, utilization, including controls, statistical data analysis, problem descriptions unique to a particular application, and bioprocess economic analyses. The journal publishes reviews deemed of interest to readers, as well as book reviews, meeting and symposia notices, and news items relating to biotechnology in both the industrial and academic communities.
In addition, Applied Biochemistry and Biotechnology often publishes lists of patents and publications of special interest to readers.
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