A Genomics Based Discovery of Secondary Metabolite Biosynthetic Gene Clusters in <i>Aspergillus ustus</i>

Secondary metabolites (SMs) produced by Aspergillus have been extensively studied for their crucial roles in human health, medicine and industrial production. However, the resulting information is almost exclusively derived from a few model organisms, including A. nidulans and A. fumigatus, but little is known about rare pathogens. In this study, we performed a genomics based discovery of SM biosynthetic gene clusters in Aspergillus ustus, a rare human pathogen. A total of 52 gene clusters were identified in the draft genome of A. ustus 3.3904, such as the sterigmatocystin biosynthesis pathway that was commonly found in Aspergillus species. In addition, several SM biosynthetic gene clusters were firstly identified in Aspergillus that were possibly acquired by horizontal gene transfer, including the vrt cluster that is responsible for viridicatumtoxin production. Comparative genomics revealed that A. ustus shared the largest number of SM biosynthetic gene clusters with A. nidulans, but much fewer with other Aspergilli like A. niger and A. oryzae. These findings would help to understand the diversity and evolution of SM biosynthesis pathways in genus Aspergillus, and we hope they will also promote the development of fungal identification methodology in clinic.曲霉属（Aspergillus）真菌产生的次级代谢产物（Secondary metabolites, SMs）因其在人类健康、医药及工业生产中的关键作用而被广泛研究。然而，现有相关研究信息几乎仅来自少数模式菌株，包括构巢曲霉（A. nidulans）和烟曲霉（A. fumigatus），而对于罕见致病曲霉的了解却十分匮乏。本研究以罕见人类致病菌臭曲霉（Aspergillus ustus）为研究对象，开展了基于基因组学的次级代谢产物生物合成基因簇挖掘工作。研究团队在臭曲霉3.3904的草图基因组（draft genome）中共鉴定得到52个基因簇，其中包括在曲霉属中广泛分布的柄曲霉素（sterigmatocystin）生物合成通路。此外，本研究还首次在曲霉属中发现数个可能通过水平基因转移（horizontal gene transfer）获得的次级代谢产物生物合成基因簇，其中包括负责合成维里卡坦毒素（viridicatumtoxin）的vrt基因簇。比较基因组学（Comparative genomics）分析显示，臭曲霉与构巢曲霉（A. nidulans）共享的次级代谢产物生物合成基因簇数量最多，而与黑曲霉（A. niger）、米曲霉（A. oryzae）等其他曲霉的共享基因簇数量则少得多。本研究结果有助于解析曲霉属次级代谢产物生物合成通路的多样性与演化历程，同时有望推动临床真菌鉴定方法的发展。