Zhang Tao, Feng Jianjv, He Wenni, Rong Xiaoting, Lv Hui, Li Jun, Li Xinxin, Wang Hao, Wang Lu, Zhang Lixin, Yu Liyan
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai 200237, China.
J Fungi (Basel). 2023 Apr 17;9(4):481. doi: 10.3390/jof9040481.
Terpenoids constitute a structurally diverse class of secondary metabolites with wide applications in the pharmaceutical, fragrance and flavor industries. CPCC 401429 is a basidiomycetous mushroom that could produce anti-tumor melleolides. To date, no studies have been conducted to thoroughly investigate the sesquiterpenes biosynthetic potential in or related genus. This study aims to unravel the phylogeny, terpenome, and functional characterization of unique sesquiterpene biosynthetic genes of the strain CPCC 401429. Herein, we report the genome of the fungus containing 15,145 protein-encoding genes. MLST-based phylogeny and comparative genomic analyses shed light on the precise reclassification of . suggesting that it belongs to the genus . Gene ontology enrichment and pathway analyses uncover the hidden capacity for producing polyketides and terpenoids. Genome mining directed predictive framework reveals a diverse network of sesquiterpene synthases (STSs). Among twelve putative STSs encoded in the genome, six ones are belonging to the novel minor group: diverse Clade IV. In addition, RNA-sequencing based transcriptomic profiling revealed differentially expressed genes (DEGs) of the fungus CPCC 401429 in three different fermentation conditions, that of which enable us to identify noteworthy genes exemplified as STSs coding genes. Among the ten sesquiterpene biosynthetic DEGs, two genes including and were selected for functional characterization. Yeast cells expressing DtSTS9 and DtSTS10 could produce diverse sesquiterpene compounds, reinforced that STSs in the group Clade IV might be highly promiscuous producers. This highlights the potential of in generating novel terpenoids. To summarize, our analyses will facilitate our understanding of phylogeny, STSs diversity and functional significance of species. These results will encourage the scientific community for further research on uncharacterized STSs of Basidiomycota phylum, biological functions, and potential application of this vast source of secondary metabolites.
萜类化合物是一类结构多样的次生代谢产物，在制药、香料和香精行业有着广泛应用。CPCC 401429是一种担子菌蘑菇，能够产生抗肿瘤蜜环菌素。迄今为止，尚未开展研究全面探究该属或相关属中倍半萜生物合成潜力。本研究旨在揭示CPCC 401429菌株独特倍半萜生物合成基因的系统发育、萜类组学及功能特征。在此，我们报道了该真菌的基因组，其包含15145个蛋白质编码基因。基于多位点序列分型的系统发育分析和比较基因组分析为该菌株的精确重新分类提供了线索，表明它属于某属。基因本体富集分析和通路分析揭示了其产生聚酮化合物和萜类化合物的潜在能力。基因组挖掘导向的预测框架揭示了一个多样的倍半萜合酶（STS）网络。在基因组中编码的12个假定STS中，有6个属于新的小类：不同的进化枝IV。此外，基于RNA测序的转录组分析揭示了CPCC 401429真菌在三种不同发酵条件下的差异表达基因（DEG），这使我们能够鉴定出值得关注且以STS编码基因为例的基因。在10个倍半萜生物合成DEG中，选择了包括某基因和某基因在内的2个基因进行功能表征。表达DtSTS9和DtSTS10的酵母细胞能够产生多种倍半萜化合物，这强化了进化枝IV组中的STS可能是高度混杂生产者的观点。这突出了该菌株在生成新型萜类化合物方面的潜力。总之，我们的分析将有助于我们理解该菌株的系统发育、STS多样性及功能意义。这些结果将鼓励科学界进一步研究担子菌门未表征的STS、其生物学功能以及这一丰富次生代谢产物来源的潜在应用。
