Production of Pyomelanin, a Second Type of Melanin, via the Tyrosine Degradation Pathway in Aspergillus fumigatus
Production of Pyomelanin, a Second Type of Melanin, via the Tyrosine Degradation Pathway in Aspergillus fumigatus
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DOI：
10.1128/aem.02077-08
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发表时间：
2009-01-15
影响因子：
4.4
通讯作者：
Brakhage, Axel A.
中科院分区：
文献类型：
--
作者：
Schmaler-Ripcke, Jeannette;Sugareva, Venelina;Brakhage, Axel A.
烟曲霉是免疫抑制人群中最重要的空气传播真菌病原体。A.烟曲霉能够产生主要存在于分生孢子中的二羟基萘黑色素。它的生物合成是一个重要的毒力决定因素。在这里，我们表明，A.烟曲霉能够产生替代的黑色素，即，脓黑素，通过不同的途径，从L-酪氨酸开始。蛋白质组分析表明，L-酪氨酸降解酶的合成时，真菌生长与L-酪氨酸在培养基中。为了详细研究该途径，我们删除了编码色素产生必需酶的基因，尿黑酸双加氧酶（hmgA）和4-羟苯基丙酮酸双加氧酶（hppD）。合成的脓黑素与从A.烟曲霉培养物证实所观察到的色素为脓黑素。在hmgA缺失菌株中，HmgA活性被废除，尿黑酸的积累引起色素形成增加。相反，尿黑酸和脓黑素没有观察到与hppD缺失突变体。hppD缺失突变体的幼苗表现出对活性氧中间体的敏感性增加。这两个研究基因的转录诱导L-酪氨酸。这些结果证实了缺失基因的功能和预测的途径。烟熏。高锰酸是主要的中间体，导致脓黑素的L-酪氨酸降解途径与人类中导致碱性黑素的途径相似。
Aspergillus fumigatus is the most important airborne fungal pathogen of immunosuppressed humans. A. fumigatus is able to produce dihydroxynaphthalene melanin, which is predominantly present in the conidia. Its biosynthesis is an important virulence determinant. Here, we show that A. fumigatus is able to produce an alternative melanin, i.e., pyomelanin, by a different pathway, starting from L-tyrosine. Proteome analysis indicated that the L-tyrosine degradation enzymes are synthesized when the fungus is grown with L-tyrosine in the medium. To investigate the pathway in detail, we deleted the genes encoding essential enzymes for pigment production, homogentisate dioxygenase (hmgA) and 4-hydroxyphenylpyruvate dioxygenase (hppD). Comparative Fourier transform infrared spectroscopy of synthetic pyomelanin and pigment extracted from A. fumigatus cultures confirmed the identity of the observed pigment as pyomelanin. In the hmgA deletion strain, HmgA activity was abolished and the accumulation of homogentisic acid provoked an increased pigment formation. In contrast, homogentisic acid and pyomelanin were not observed with an hppD deletion mutant. Germlings of the hppD deletion mutant showed an increased sensitivity to reactive oxygen intermediates. The transcription of both studied genes was induced by L-tyrosine. These results confirmed the function of the deleted genes and the predicted pathway in A. fumigatus. Homogentisic acid is the major intermediate, and the L-tyrosine degradation pathway leading to pyomelanin is similar to that in humans leading to alkaptomelanin.