Genome of the endophytic fungus Fusarium sp. VM-40 isolated from Vinca minor

The genus of Fusarium is well-known to comprise many plant pathogenic fungi that affect cereal crops worldwide, causing severe damage to agriculture and the economy. In this study, an endophytic fungus designated as Fusarium sp. VM-40 was isolated from the traditional European medicinal plant Vinca minor. Our morphological characterization and phylogenetic analysis reveal that Fusarium sp. VM-40 is closely related to Fusarium paeoniae, belonging to the F. tricinctum species complex (FTSC), the genomic architecture and secondary metabolite profile of which have not been investigated. Thus, we sequenced the whole genome of Fusarium sp. VM- 40 with the new Oxford Nanopore R10.4 flowcells. The assembled genome is 40 Mb in size with a GC content of 47.72%, 15 contigs (>= 50000 bp; N50~4.3 Mb), and 13,546 protein-coding genes, 691 of which are carbohydrate-active enzymes (CAZymes)-encoding genes. We furthermore predicted a total of 56 biosynthetic gene clusters (BGCs) with antiSMASH, 25 of which showed similarity with known BGCs. In addition, we explored the potential for this fungus to produce secondary metabolites by untargeted metabolomics. Our analyses reveal that this fungus produces a rich source of antifungal (e.g. oxysporidinone), antibacterial (e.g. aurofusarin, enniatins), and anticancer (e.g. beta-elemene) metabolites. We also employed an epigenetic manipulation method to activate cryptic BGCs. Some previously unidentified compounds are observed in media spiked with sodium butyrate. Taken together, this study provides systematic research on the whole genome sequence, biosynthetic potential, and metabolome of the endophytic fungus Fusarium sp. VM-40.

镰孢菌属（Fusarium）是一类广为人知的植物病原真菌类群，其成员可侵染全球多种谷类作物，对农业生产与经济发展造成严重危害。本研究从欧洲传统药用植物小蔓长春花（Vinca minor）中分离得到一株内生真菌，命名为镰孢菌属未定种（Fusarium sp.）VM-40。通过形态学表征与系统发育分析，我们发现VM-40与芍药镰孢菌（Fusarium paeoniae）亲缘关系紧密，二者同属于三线镰孢菌种复合体（FTSC），目前学界尚未对该复合体的基因组架构与次级代谢产物谱展开研究。为此，我们采用新一代牛津纳米孔（Oxford Nanopore）R10.4测序芯片对VM-40的全基因组进行了测序。组装完成的基因组大小为40 Mb，GC含量为47.72%，共得到15条长度≥50000 bp的重叠群（contig），重叠群N50值约为4.3 Mb，共注释得到13546个蛋白质编码基因，其中691个为碳水化合物活性酶（CAZymes）编码基因。此外，我们借助antiSMASH工具共预测得到56个生物合成基因簇（BGCs），其中25个与已知生物合成基因簇具有同源相似性。另外，我们通过非靶向代谢组学技术探究了该真菌的次级代谢产物合成潜力，分析结果显示该真菌可产生多种活性代谢产物：包括抗真菌类（如氧孢菌素（oxysporidinone））、抗菌类（如金色菌素（aurofusarin）、恩镰孢菌素（enniatins））以及抗癌类（如β-榄香烯（beta-elemene））代谢产物。我们还采用表观遗传调控手段激活了该真菌的隐蔽型生物合成基因簇，在添加丁酸钠的培养基中检测到了若干此前未被鉴定的代谢产物。综上，本研究针对内生真菌镰孢菌属未定种VM-40的全基因组序列、生物合成潜力以及代谢组学特征开展了系统性研究。