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人类致病真菌中的非核糖体肽合成酶基因簇

Non-ribosomal Peptide Synthetase Gene Clusters in the Human Pathogenic Fungus .

作者信息

Le Govic Yohann, Papon Nicolas, Le Gal Solène, Bouchara Jean-Philippe, Vandeputte Patrick

机构信息

Groupe d'Etude des Interactions Hôte-Pathogène (GEIHP, EA 3142), SFR ICAT 4208, Université d'Angers, Angers, France.

Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire, Université d'Angers, Angers, France.

出版信息

Front Microbiol. 2019 Sep 4;10:2062. doi: 10.3389/fmicb.2019.02062. eCollection 2019.

Abstract

species are opportunistic fungi which preferentially affect patients with underlying conditions such as immunosuppression or cystic fibrosis (CF). While being the second most common molds capable to chronically colonize the CF lungs, the natural history of infection remains unclear. In filamentous fungi, a broad range of important secondary metabolites that are recognized as virulence factors are produced by multidomain non-ribosomal peptide synthetases (NRPSs). The aim of this study was to provide a global analysis of NRPS-encoding genes based on the recently sequenced genome. We uncovered a total of nine NRPS genes, of which six exhibited sufficient similarity scores with other fungal NRPSs to predict the class of the generated peptide: siderophores ( = 2), epidithiodioxopiperazines ( = 2), and cyclopeptides ( = 2). Phylogenetic trees based on the multiple alignments of adenylation (A) domain sequences corroborated these findings. Nevertheless, substrate prediction methods for NRPS A-domains tended to fail, thus questioning about the exact nature of the peptide produced. Further studies should be undertaken since NRPSs, which are not synthesized by human cells, could represent attractive therapeutic targets.

摘要

该菌种属于机会性真菌,主要感染患有免疫抑制或囊性纤维化(CF)等基础疾病的患者。作为第二常见的能够长期定植于CF肺部的霉菌,其感染的自然史仍不清楚。在丝状真菌中,多结构域非核糖体肽合成酶(NRPSs)可产生多种被认为是毒力因子的重要次生代谢产物。本研究的目的是基于最近测序的基因组对NRPS编码基因进行全面分析。我们共发现了9个NRPS基因,其中6个与其他真菌NRPSs具有足够相似的得分,以预测所产生肽的类别:铁载体(=2)、环二硫代二氧哌嗪(=2)和环肽(=2)。基于腺苷化(A)结构域序列多重比对的系统发育树证实了这些发现。然而,NRPS A结构域的底物预测方法往往失败,因此对所产生肽的确切性质提出了质疑。由于NRPSs不是由人类细胞合成的,可能是有吸引力的治疗靶点,因此应进一步开展研究。

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