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通过对 6 个不同物种的基因组测序,将次生代谢物与基因簇联系起来。

Linking secondary metabolites to gene clusters through genome sequencing of six diverse species.

机构信息

Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Lyngby, Denmark.

US Department of Energy Joint Genome Institute, Walnut Creek, CA 94598.

出版信息

Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E753-E761. doi: 10.1073/pnas.1715954115. Epub 2018 Jan 9.

Abstract

The fungal genus of is highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse species (, , , and ) have been whole-genome PacBio sequenced to provide genetic references in three sections. and also were sequenced for SM elucidation. Thirteen genomes were analyzed with comparative genomics to determine phylogeny and genetic diversity, showing that each presented genome contains 15-27% genes not found in other sequenced Aspergilli. In particular, was compared with the pathogenic species This suggests that can produce most of the same allergens, virulence, and pathogenicity factors as , suggesting that could be as pathogenic as Furthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences, and predictive algorithms. We thus identify putative SM clusters for aflatoxin, chlorflavonin, and ochrindol in , , and , respectively, and novofumigatonin, -cycloechinulin, and -aszonalenins in Our study delivers six fungal genomes, showing the large diversity found in the genus; highlights the potential for discovery of beneficial or harmful SMs; and supports reports of pathogenicity. It also shows how biological, biochemical, and genomic information can be combined to identify genes involved in the biosynthesis of specific SMs.

摘要

是一种非常有趣的真菌属,包含了从工业细胞工厂、模式生物到人类病原体的各种生物。特别是,这个群体拥有丰富的生物活性次生代谢产物(SMs)的产生。在这项工作中,我们对四个不同的 种( 、 、 、和 )进行了全基因组 PacBio 测序,为三个部分提供了遗传参考。和 也进行了 SM 阐明的测序。对 13 个基因组进行了比较基因组学分析,以确定系统发育和遗传多样性,结果表明,每个基因组都包含 15-27%未在其他已测序的曲霉菌中发现的基因。特别是,与致病性物种 进行了比较。这表明 可以产生与 相同的过敏原、毒力和致病性因素,这表明 可能与 一样具有致病性。此外,根据生物和化学知识以及分析、基因组序列和预测算法,将 SMs 与基因簇相关联。因此,我们分别在 、 、 和 中鉴定出了黄曲霉毒素、氯黄酮和ochrindol 的推定 SM 簇,以及 、 -cycloechinulin 和 -aszonalenins 的推定 SM 簇。我们的研究提供了六个真菌基因组,展示了 属中发现的巨大多样性;强调了发现有益或有害 SMs 的潜力;并支持 致病性的报告。它还展示了如何将生物、生化和基因组信息结合起来,以鉴定参与特定 SM 生物合成的基因。

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Whole genome comparison of the A. fumigatus family.烟曲霉家族的全基因组比较。
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