{"title":"Gene Mining and Optimization of the Biosynthesis of Cannabidiol in <i>Fusarium solani</i> XG4-2.","authors":"Jiale Cui, Wenbo Wu, Shun Zhang, Shang Li, Changyixin Xiao, Sujuan Cui, Zichang Lu, Mengran Zhan, Yuzhe Ren, Yang Xie, Yunfeng Zhang, Xiaozhou Luo, Jing Yin","doi":"10.1021/acs.jnatprod.5c00298","DOIUrl":null,"url":null,"abstract":"<p><p>Cannabidiol (CBD) exhibits various pharmacological properties, including antidepressant, antioxidant, antipsychotic, analgesic, and neuroprotective effects. However, the low natural yields of CBD and the restricted biosynthetic pathways currently limit its commercial viability and demand in the marketplace. This study evaluated the potential of 101 endophytic fungi from <i>Cannabis sativa</i> for biotransformation and CBD synthesis. Notably, strain XG4-2 (CGMCC 40476) stably produced 50.07 μg/L CBD in a basic medium and shared 99.42% ITS sequence homology with <i>Fusarium solani</i>, representing the first endophytic fungal reported to synthesize CBD. To enhance CBD production, a triple-strategy approach was implemented, comprising cocultivation with engineered <i>Saccharomyces cerevisiae</i>, optimization of fermentation conditions, and the addition of host-derived plant inducers. This integrated strategy led to a significant increase in CBD yield, reaching 526.9 μg/L, a 9.52-fold enhancement compared to the initial output. Whole-genome sequencing of XG4-2 revealed 44 putative secondary metabolite biosynthetic gene clusters and 23 genes potentially involved in CBD biosynthesis, indicating a unique metabolic pathway distinct from that of plants. This study demonstrates a novel approach for microbial CBD production by leveraging endophytic fungal resources, cocultivation strategies, fermentation optimization, and gene discovery. The findings provide a foundation for sustainable and efficient biotechnological production of CBD.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.5c00298","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Cannabidiol (CBD) exhibits various pharmacological properties, including antidepressant, antioxidant, antipsychotic, analgesic, and neuroprotective effects. However, the low natural yields of CBD and the restricted biosynthetic pathways currently limit its commercial viability and demand in the marketplace. This study evaluated the potential of 101 endophytic fungi from Cannabis sativa for biotransformation and CBD synthesis. Notably, strain XG4-2 (CGMCC 40476) stably produced 50.07 μg/L CBD in a basic medium and shared 99.42% ITS sequence homology with Fusarium solani, representing the first endophytic fungal reported to synthesize CBD. To enhance CBD production, a triple-strategy approach was implemented, comprising cocultivation with engineered Saccharomyces cerevisiae, optimization of fermentation conditions, and the addition of host-derived plant inducers. This integrated strategy led to a significant increase in CBD yield, reaching 526.9 μg/L, a 9.52-fold enhancement compared to the initial output. Whole-genome sequencing of XG4-2 revealed 44 putative secondary metabolite biosynthetic gene clusters and 23 genes potentially involved in CBD biosynthesis, indicating a unique metabolic pathway distinct from that of plants. This study demonstrates a novel approach for microbial CBD production by leveraging endophytic fungal resources, cocultivation strategies, fermentation optimization, and gene discovery. The findings provide a foundation for sustainable and efficient biotechnological production of CBD.
期刊介绍：
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
