生物
次生代谢
次生代谢物
基因簇
青霉属
聚酮合酶
聚酮
基因组
细菌
核糖体RNA
基因
生物合成
遗传学
计算生物学
作者
Jens Nielsen,Sietske Grijseels,Sylvain Prigent,Boyang Ji,Jacques Dainat,Kristian Fog Nielsen,Jens C. Frisvad,Mhairi Workman,Jens Nielsen
出处
期刊:Nature microbiology
日期:2017-04-03
卷期号:2 (6)
被引量:223
标识
DOI:10.1038/nmicrobiol.2017.44
摘要
Filamentous fungi produce a wide range of bioactive compounds with important pharmaceutical applications, such as antibiotic penicillins and cholesterol-lowering statins. However, less attention has been paid to fungal secondary metabolites compared to those from bacteria. In this study, we sequenced the genomes of 9 Penicillium species and, together with 15 published genomes, we investigated the secondary metabolism of Penicillium and identified an immense, unexploited potential for producing secondary metabolites by this genus. A total of 1,317 putative biosynthetic gene clusters (BGCs) were identified, and polyketide synthase and non-ribosomal peptide synthetase based BGCs were grouped into gene cluster families and mapped to known pathways. The grouping of BGCs allowed us to study the evolutionary trajectory of pathways based on 6-methylsalicylic acid (6-MSA) synthases. Finally, we cross-referenced the predicted pathways with published data on the production of secondary metabolites and experimentally validated the production of antibiotic yanuthones in Penicillia and identified a previously undescribed compound from the yanuthone pathway. This study is the first genus-wide analysis of the genomic diversity of Penicillia and highlights the potential of these species as a source of new antibiotics and other pharmaceuticals.
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