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An interpreted atlas of biosynthetic gene clusters from 1,000 fungal genomes [Biochemistry]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-05-11 , DOI: 10.1073/pnas.2020230118
Matthew T. Robey, Lindsay K. Caesar, Milton T. Drott, Nancy P. Keller, Neil L. Kelleher

Fungi are prolific producers of natural products, compounds which have had a large societal impact as pharmaceuticals, mycotoxins, and agrochemicals. Despite the availability of over 1,000 fungal genomes and several decades of compound discovery efforts from fungi, the biosynthetic gene clusters (BGCs) encoded by these genomes and the associated chemical space have yet to be analyzed systematically. Here, we provide detailed annotation and analyses of fungal biosynthetic and chemical space to enable genome mining and discovery of fungal natural products. Using 1,037 genomes from species across the fungal kingdom (e.g., Ascomycota, Basidiomycota, and non-Dikarya taxa), 36,399 predicted BGCs were organized into a network of 12,067 gene cluster families (GCFs). Anchoring these GCFs with reference BGCs enabled automated annotation of 2,026 BGCs with predicted metabolite scaffolds. We performed parallel analyses of the chemical repertoire of fungi, organizing 15,213 fungal compounds into 2,945 molecular families (MFs). The taxonomic landscape of fungal GCFs is largely species specific, though select families such as the equisetin GCF are present across vast phylogenetic distances with parallel diversifications in the GCF and MF. We compare these fungal datasets with a set of 5,453 bacterial genomes and their BGCs and 9,382 bacterial compounds, revealing dramatic differences between bacterial and fungal biosynthetic logic and chemical space. These genomics and cheminformatics analyses reveal the large extent to which fungal and bacterial sources represent distinct compound reservoirs. With a >10-fold increase in the number of interpreted strains and annotated BGCs, this work better regularizes the biosynthetic potential of fungi for rational compound discovery.



中文翻译:

一千个真菌基因组生物合成基因簇的解释图集[生物化学]

真菌是天然产物的多产者,天然产物是对社会产生重大影响的化合物,如药物,霉菌毒素和农用化学品。尽管有超过1,000种真菌基因组可用,而且真菌已进行了数十年的化合物发现工作,但由这些基因组编码的生物合成基因簇(BGC)和相关的化学空间尚未得到系统的分析。在这里,我们提供了真菌生物合成和化学空间的详细注释和分析,以使基因组挖掘和真菌天然产物的发现成为可能。使用来自整个真菌界物种(例如,子囊菌,担子菌属和非Dikarya分类群)的1,037个基因组,将36,399个预测的BGC组成了一个由12,067个基因簇家族(GCF)组成的网络。将这些GCF与参考BGC固定在一起后,便可以自动注释2,026个BGC与预测的代谢物支架。我们对真菌的化学组成进行了平行分析,将15,213种真菌化合物整理为2,945个分子家族(MF)。真菌GCF的分类学景观在很大程度上是特定物种的,尽管在GCF和MF中跨越宽阔的系统发育距离存在着类似的家族,例如Equisetin GCF。我们将这些真菌数据集与一组5,453个细菌基因组及其BGC和9,382个细菌化合物进行了比较,揭示了细菌和真菌的生物合成逻辑和化学空间之间的巨大差异。这些基因组学和化学信息学分析表明,真菌和细菌来源在很大程度上代表了独特的化合物储集层。随着解释菌株和带注释的BGC数量的增加> 10倍,

更新日期:2021-05-03
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