Nitrogen regulator GInR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes
Nitrogen regulator GInR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes
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氮调节剂 GlnR 控制放线菌对非磷酸转移酶系统碳源的吸收和利用
DOI：
10.1073/pnas.1508465112
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发表时间：
2015-12-22
影响因子：
11.1
通讯作者：
Ye, Bang-Ce
中科院分区：
文献类型：
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作者：
Liao, Cheng-Heng;Yao, Lili;Ye, Bang-Ce
放线菌对多种碳水化合物的吸收和利用的调节机制仍然知之甚少。在这项研究中，我们证明了GlnR(氮代谢中枢调节因子)是氮代谢的通用调节因子，在控制放线菌中非磷酸转移酶系统(PTS)碳源的运输中扮演着一个以前未知的重要角色。已观察到GlnR可以直接与大多数(20个中的13个)碳水化合物三磷酸腺苷结合盒(ABC)转运子基因的启动子相互作用，并能激活这些基因的转录，以响应氮的供应，在工业生产红霉素的红多孢菌中。在所使用的培养条件下，glnR基因的缺失导致严重的生长迟缓，选择ABC运输的碳水化合物(麦芽糖、山梨醇、甘露醇、纤维二糖、海藻糖或甘露糖)作为唯一的碳源。此外，我们发现GlnR介导的碳水化合物运输调节在放线菌中是高度保守的。这些结果表明，GlnR的作用超越了氮代谢，介导了碳代谢中的关键功能，以及响应细胞营养状态的氮和碳代谢途径的串扰。这些发现为非PTS碳水化合物的运输和代谢的分子调控提供了洞察力，并揭示了生物质衍生糖在生物燃料和生物化学品生产中的潜在应用。
The regulatory mechanisms underlying the uptake and utilization of multiple types of carbohydrates in actinomycetes remain poorly understood. In this study, we show that GlnR (central regulator of nitrogen metabolism) serves as a universal regulator of nitrogen metabolism and plays an important, previously unknown role in controlling the transport of non-phosphotransferase-system (PTS) carbon sources in actinomycetes. It was observed that GlnR can directly interact with the promoters of most (13 of 20) carbohydrate ATP-binding cassette (ABC) transporter loci and can activate the transcription of these genes in response to nitrogen availability in industrial, erythromycin-producing Saccharopolyspora erythraea. Deletion of the glnR gene resulted in severe growth retardation under the culture conditions used, with select ABC-transported carbohydrates (maltose, sorbitol, mannitol, cellobiose, trehalose, or mannose) used as the sole carbon source. Furthermore, we found that GlnR-mediated regulation of carbohydrate transport was highly conserved in actinomycetes. These results demonstrate that GlnR serves a role beyond nitrogen metabolism, mediating critical functions in carbon metabolism and crosstalk of nitrogen-and carbon-metabolism pathways in response to the nutritional states of cells. These findings provide insights into the molecular regulation of transport and metabolism of non-PTS carbohydrates and reveal potential applications for the cofermentation of biomass-derived sugars in the production of biofuels and bio-based chemicals.