Phylogenomic analysis of non-ribosomal peptide synthetases in the genus Aspergillus

Phylogenomic analysis of non-ribosomal peptide synthetases in the genus Aspergillus
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DOI:
10.1016/j.gene.2006.07.008
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发表时间:
2006-11-15
期刊:
影响因子:
3.5
通讯作者:
Perfect, John R.
Perfect, John R.
中科院分区:
生物学3区
文献类型:
--
作者:
Cramer, Robert A., Jr.;Stajich, Jason E.;Perfect, John R.

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来自曲霉属的真菌是重要的寄生菌和机会性人类真菌病原体,其以这些和其他不同的方式对人类健康做出贡献。它们对人类福祉的部分影响源于小分子量次级代谢产物的产生,这可能有助于这些真菌引起侵袭性真菌感染和过敏性疾病的能力。在这项研究中,我们确定了一组酶,负责在五个曲霉属物种的次生代谢产物的生产,非核糖体肽合成酶(NRPS)。利用隐马尔可夫模型对A. funtigatus、黑腹拟步行虫A. Flavus、黄毛菊A. terreus,刺毛菊A. nidulans和A. NRPS蛋白中保守结构域的序列。利用腺苷酸化结构域的系谱来鉴定所检查的曲霉属物种中的正向和独特的NRPS,以及获得对曲霉NRPS的潜在进化的理解。A.中鉴定的14个NRPS的mRNA丰度。在不同环境条件下,利用实时荧光定量PCR技术对鱼形目基因组进行分析,初步了解NRPSs肽产物的可能功能。我们的研究结果表明,曲霉属物种包含保守和独特的NRPS基因具有复杂的进化历史。这一结果表明,曲霉属产生的非核糖体合成肽的实质性的多样性。对这些基因及其肽产物的进一步分析可以确定NRPS产生的次级代谢产物在曲霉生理学、生态学和真菌致病性中的重要作用。(c)2006 Elsevier B.V.保留所有权利。
Fungi from the genus Aspergillus are important saprophytes and opportunistic human fungal pathogens that contribute in these and other diverse ways to human well-being. Part of their impact on human well-being stems from the production of small molecular weight secondary metabolites, which may contribute to the ability of these fungi to cause invasive fungal infections and allergic diseases. In this study, we identified one group of enzymes responsible for secondary metabolite production in five Aspergillus species, the non-ribosomal peptide synthetases (NRPS). Hidden Markov models were used to search the genome databases of A. funtigatus, A. flavus, A. terreus, A. nidulans, and A. oryzae for domains conserved in NRPS proteins. A genealogy of adenylation domains was utilized to identify orthologous and unique NRPS among the Aspergillus species examined, as well as gain an understanding of the potential evolution of Aspergillus NRPS. mRNA abundance of the 14 NRPS identified in the A. Jumigatus genome was analyzed using real-time reverse transcriptase PCR in different environmental conditions to gain a preliminary understanding of the possible functions of the NRPSs' peptide products. Our results suggest that Aspergillus species contain conserved and unique NRPS genes with a complex evolutionary history. This result suggests that the genus Aspergillus produces a substantial diversity of nonribosomally synthesized peptides. Further analysis of these genes and their peptide products may identify important roles for secondary metabolites produced by NRPS in Aspergillus physiology, ecology, and fungal pathogenicity. (c) 2006 Elsevier B.V. All rights reserved.