Biosynthesis of UDP-4-keto-6-deoxyglucose and UDP-rhamnose in Pathogenic Fungi Magnaporthe grisea and Botryotinia fuckeliana
Biosynthesis of UDP-4-keto-6-deoxyglucose and UDP-rhamnose in Pathogenic Fungi Magnaporthe grisea and Botryotinia fuckeliana
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DOI：
10.1074/jbc.m111.287367
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发表时间：
2012-01-06
影响因子：
4.8
通讯作者：
Bar-Peled, Maor
中科院分区：
文献类型：
--
作者：
Martinez, Viviana;Ingwers, Miles;Bar-Peled, Maor
越来越多的证据表明，在几种真菌中，含鼠李糖的聚糖参与影响宿主-病原体相互作用的过程，包括粘附、识别、毒力和生物膜形成。然而，很少有人知道这些聚糖的合成途径。我们表明，鼠李糖是存在于从水稻病原体稻瘟病菌和植物病原体Botryotinia fuckeliana分离的聚糖。我们还提供了这些真菌产生UDP-鼠李糖的证据。这与细菌相反，其中dTDP-鼠李糖是这种糖的活化形式。在细菌中，dGDP-鼠李糖的形成需要三种酶。在这里，我们证明，在真菌中，只有两个基因所需的UDP-Rha合成。第一个基因编码UDP-葡萄糖-4，6-脱氢酶，其将UDP-葡萄糖转化为UDP-4-酮-6-脱氧葡萄糖。通过时间分辨H-1 NMR光谱显示产物主要以水合形式沿着少量酮形式存在于溶液中。第二个基因编码双功能UDP-4-酮-6-脱氧葡萄糖-3，5-差向异构酶/-4-还原酶，其将UDP-4-酮-6-脱氧葡萄糖转化为UDP-鼠李糖。糖组成分析和不同生长阶段的基因表达研究表明，含鼠李糖聚糖的合成是在组织特异性调节下进行的。总之，我们的研究结果提供了新的见解含鼠李糖聚糖在真菌的生命周期的形成。这些聚糖在真菌病原体和它们的宿主之间的相互作用的作用进行了讨论。了解含鼠李糖聚糖形成过程中涉及的代谢途径可能有助于开发治疗人类真菌疾病的药物，因为据我们所知，哺乳动物不会产生这些类型的聚糖。
There is increasing evidence that in several fungi, rhamnose-containing glycans are involved in processes that affect hostpathogen interactions, including adhesion, recognition, virulence, and biofilm formation. Nevertheless, little is known about the pathways for the synthesis of these glycans. We show that rhamnose is present in glycans isolated from the rice pathogen Magnaporthe grisea and from the plant pathogen Botryotinia fuckeliana. We also provide evidence that these fungi produce UDP-rhamnose. This is in contrast to bacteria where dTDP-rhamnose is the activated form of this sugar. In bacteria, formation of dTDP-rhamnose requires three enzymes. Here, we demonstrate that in fungi only two genes are required for UDP-Rha synthesis. The first gene encodes a UDP-glucose-4,6-dehydratase that converts UDP-glucose to UDP-4-keto-6-deoxyglucose. The product was shown by time-resolved H-1 NMR spectroscopy to exist in solution predominantly as a hydrated form along with minor amounts of a keto form. The second gene encodes a bifunctional UDP-4-keto-6-deoxyglucose-3,5-epimerase/-4-reductase that converts UDP-4-keto-6-deoxyglucose to UDP-rhamnose. Sugar composition analysis and gene expression studies at different stages of growth indicate that the synthesis of rhamnose-containing glycans is under tissue-specific regulation. Together, our results provide new insight into the formation of rhamnose-containing glycans during the fungal life cycle. The role of these glycans in the interactions between fungal pathogens and their hosts is discussed. Knowledge of the metabolic pathways involved in the formation of rhamnose-containing glycans may facilitate the development of drugs to combat fungal diseases in humans, as to the best of our knowledge mammals do not make these types of glycans.