华东理工大学生物反应器工程国家重点实验室教授叶邦策团队完成一项研究，揭示了氮代谢调控蛋白GlnR是放线菌多糖转运及利用系统的重要调控因子。相关研究成果日前在线发表于《美国科学院院报》。

据介绍，微生物对营养物质的利用具有偏好性，当培养基中存在多种碳源时，微生物会选择先利用易于分解的碳源物质，然后再利用其他碳源。由于在实际产业制造中，微生物的“食物”基本都是生物质降解形成的混合糖类，这种依次利用的代谢产物阻遏效应（CCR）就严重阻碍了生物质多糖的高效利用，由此也形成了阻碍生产效率提升的瓶颈。

“要打破CCR效应，纠正微生物的偏食陋习，就要从系统层次揭示它的作用机制，通过基因工程手段，把生物质来源的六碳糖和五碳糖的顺序利用改变为同时利用，这样就可以提高生物质的转化及利用效率，这也是当前生物制造的重要研究课题之一。”叶邦策表示。

该成果以放线菌为研究对象，对其摄取和利用多种营养物质（氮源、碳源及磷源）的调控机制进行研究，通过构建新型生物传感器，在线监测微生物细胞内的代谢状态，建立了碳、氮、磷交叉调控网络，首次揭示了氮代谢调控蛋白GlnR是放线菌多糖转运及利用系统的重要调控因子。专家认为，由于放线菌在生物制造中应用极为广泛，此发现有望大幅度提高相关生物制造产业的效率。（来源：中国科学报 黄辛 房树芬）

Nitrogen regulator GlnR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes

Abstract  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.

原文链接：http://www.pnas.org/content/112/51/15630.full.pdf