Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates
Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates
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DOI：
10.1128/msphere.00156-20
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发表时间：
2020-03-01
期刊：
影响因子：
4.8
通讯作者：
Greco, C.
中科院分区：
文献类型：
--
作者：
Drott, M. T.;Bastos, R. W.;Greco, C.
丝状真菌尼杜拉曲霉一直是研究真菌遗传学的主要主力。这些工作主要集中在阐明生物合成基因簇(BGC)及其产生的次生代谢物(SM)的遗传学。短链霉菌既是真菌中的利基定义，又对人类具有重要的经济意义。尽管人们的注意力集中在根结线虫上，但人们对该物种中次生代谢的自然多样性知之甚少。我们测定了BGC的含量，并从两个临床分离株的全基因组序列和A4参考基因组中寻找BGC的进化模式。BGC含量的差异被用来解释用液相色谱-高分辨率质谱仪测定的SM图谱。我们发现，除了所有分离株所含的BGC的遗传变异外，还有9个BGC因存在/不存在而不同。我们在黑曲霉中发现了弧菌毒素BGC，并推测这种BGC在黑曲霉和尼杜兰特黑曲霉分离后的某个时间经历了从黑曲霉部分向青霉的水平基因转移。我们鉴定了弧菌毒素和其他几种以前未知的化合物的产生。其中一个分离株显示缺乏杂色曲霉毒素的产生，尽管它含有一个表面上完整的杂色曲霉毒素BGC，这引发了对其他已知的调控这种BGC的基因和过程的质疑。总之，我们的工作揭示了在这种遗传模式物种中BGC和SM产生的很大程度的种内多样性，并为理解次生代谢物的进化和调节提供了新的途径。重要的是，我们所知道的关于次生代谢物(SM)产生的遗传学和SM在模式真菌中的功能来自于单一的参考基因组。越来越多的研究表明，生物合成基因簇(BGC)和物种内SM多样性的重要性。然而，目前还没有关于根结线虫次生代谢的自然多样性的信息。我们发现了六个新的簇，这六个簇导致了毛状链霉菌BGC含量和SM产量的显著差异。我们描述了一组不同的突变，并强调单核苷酸多态(SNPs)、缺失和进化历史中的差异的发现如何涵盖了在非模型系统中观察到的大部分变异。我们的结果强调，根瘤假单胞菌也可能是利用种内多样性来阐明调节串扰、真菌生态学和药物发现系统的一个强有力的模型。
The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans. Differences in BGC content were used to explain SM profiles determined using liquid chromatography-high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans. One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism.IMPORTANCE Much of what we know about the genetics underlying secondary metabolite (SM) production and the function of SMs in the model fungus Aspergillus nidulans comes from a single reference genome. A growing body of research indicates the importance of biosynthetic gene cluster (BGC) and SM diversity within a species. However, there is no information about the natural diversity of secondary metabolism in A. nidulans. We discovered six novel clusters that contribute to the considerable variation in both BGC content and SM production within A. nidulans. We characterize a diverse set of mutations and emphasize how findings of single nucleotide polymorphisms (SNPs), deletions, and differences in evolutionary history encompass much of the variation observed in nonmodel systems. Our results emphasize that A. nidulans may also be a strong model to use within-species diversity to elucidate regulatory cross talk, fungal ecology, and drug discovery systems.