title: 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.
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Cheng-Heng
authors.initials: CH
authors.lastname: Liao
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Lili
authors.initials: L
authors.lastname: Yao
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Ya
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Wei-Bing
authors.initials: WB
authors.lastname: Liu
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang 832000, China bcye@ecust.edu.cn.
authors.forename: Bang-Ce
authors.initials: BC
authors.lastname: Ye
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D039903:Actinobacteria / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D008320:Maltose / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D051922:PII Nitrogen Regulatory Proteins / Q000502:physiology*; D016930:Saccharopolyspora / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D051922:PII Nitrogen Regulatory Proteins; D008320:Maltose; D002244:Carbon; D009584:Nitrogen
keywords: ABC transport system; GlnR; actinomycetes; carbon sources utilization; nitrogen metabolism