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 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 (13/20) carbohydrate 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, 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 shed insights into the molecular regulation of transport and metabolism of non-PTS carbohydrates and reveal potential applications for the co-utilization of biomass-derived sugars in the production of biofuels and bio-based chemicals.