Functional Characterization of the GlcNAc Catabolic Pathway in Cryptococcus deneoformans
Functional Characterization of the GlcNAc Catabolic Pathway in Cryptococcus deneoformans
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DOI：
10.1128/aem.00437-22
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发表时间：
2022-06-23
影响因子：
4.4
通讯作者：
Liao，Guojian
中科院分区：
文献类型：
--
作者：
Ye，Leixin;Wang，Saisai;Liao，Guojian
氨基糖N-乙酰-D-氨基葡萄糖(GlcNAc)是细胞壁成分的关键成分，在多种真菌的致病过程中起着重要作用。然而，担子菌中GlcNAc的分解代谢还没有被研究过。在这项研究中，我们在环境人类真菌病原体--齿状隐球菌中鉴定并鉴定了一个对GlcNAc利用至关重要的基因簇。The c.脱氧核糖核酸基因组包含一个GlcNAc转运体(Ngt1)、一个GlcNAc激酶(Hxk3)、一个GlcNAc-6-磷酸脱乙酰基酶(Dac1)和一个氨基葡萄糖-6-磷酸脱氨酶(NAG1)。在以GlcNAc为唯一碳源的培养体系中，它们的表达水平被高度诱导，而相应的突变体在GlcNAc的存在下表现出严重的生长缺陷。功能和生化分析表明，HXK3编码一种新的GlcNAc激酶。Hxk3保守残基的定点突变表明，ATP结合和GlcNAc结合是GlcNAc激酶活性所必需的。综上所述，本研究的结果为担子菌GlcNAc分解代谢提供了重要的见解。重要的乙酰氨基葡萄糖(GlcNAc)不仅是几丁质的组成成分，而且是真菌中重要的信号分子。GlcNAc的分解代谢途径在真菌的重要生物学过程中也起着重要作用。然而，GlcNAc在担子菌门中的利用途径尚不清楚，该门包含41,000多个物种。齿状隐球菌是一种具有代表性的担子菌病原菌，可引起危及生命的脑膜炎。在这项研究中，我们描述了一个对GlcNAc利用公司至关重要的基因簇。Deeoformans，并鉴定出一种新的GlcNAc激酶。本研究的结果为研究担子菌GlcNAc的分解代谢提供了重要的见解，并为揭示其在发病机制中的作用提供了一个起点。
The amino sugarN-acetyl-d-glucosamine (GlcNAc) is the key constituent of cell wall components and plays an important role in pathogenesis in a wide range of fungi. However, catabolism of GlcNAc has not been studied in basidiomycete fungi. In this study, we identified and characterized a gene cluster essential for GlcNAc utilization in Cryptococcus deneoformans, an environmental human fungal pathogen. TheC. deneoformansgenome contains a GlcNAc transporter (Ngt1), a GlcNAc kinase (Hxk3), a GlcNAc-6-phosphate deacetylase (Dac1), and a glucosamine-6-phosphate deaminase (Nag1). Their expression levels were highly induced in cultures containing GlcNAc as the sole carbon source, and the corresponding mutants showed severe growth defects in the presence of GlcNAc. Functional and biochemical analyses revealed thatHXK3encodes a novel GlcNAc kinase. Site-directed mutations of conserved residues of Hxk3 indicated that ATP binding and GlcNAc binding are essential for GlcNAc kinase activities. Taken together, the results from this study provide crucial insights into basidiomycete GlcNAc catabolism.IMPORTANCEN-Acetylglucosamine (GlcNAc) is recognized as not only the building block of chitin but also an important signaling molecule in fungi. The catabolic pathway of GlcNAc also plays an important role in vital biological processes in fungi. However, the utilization pathway of GlcNAc in the phylumBasidiomycota, which contains more than 41,000 species, remains unknown. Cryptococcus deneoformans is a representative basidiomycetous pathogen that causes life-threatening meningitis. In this study, we characterized a gene cluster essential for GlcNAc utilization inC. deneoformansand identified a novel GlcNAc kinase. The results of this study provide important insights into basidiomycete GlcNAc catabolism and offer a starting point for revealing its role in pathogenesis.