GlnR and PhoP regulate β-glucosidases involved in cellulose digestion in response to nitrogen and phosphate availability

The limited catalytic efficiency of cellulose-degrading enzymes restricts cellulose digestion. We investigated the transcriptional regulation of genes encoding key cellulose degrading enzymes, namely β-glucosidases, in the industrial actinobacterium Saccharopolyspora erythraea. We observed that the expression of most β-glucosidase-encoding genes was controlled by the availability of nitrogen and phosphate via their respective global regulators, namely GlnR and PhoP. Electrophoretic mobility shift assay demonstrated that GlnR and PhoP bound directly to the promoters of β-glucosidase-encoding genes. Deletion of glnR resulted in lower transcript levels and activity of β-glucosidases, leading to decreased bacterial growth on cellulose. Overexpression of glnR and phoP or nitrogen/phosphate starvation increased the transcript levels and total activity of β-glucosidases. Moreover, GlnR/PhoP-mediated cellobiose utilization was also observed in Streptomyces coelicolor A3(2). These findings provide insights into the regulatory roles played by GlnR and PhoP in coordinating nitrogen/phosphate metabolism and carbohydrate utilization, and indicate potential strategies for cellulose fermentation in the production of bio-based chemicals by actinobacteria.