GntR Family Regulator DasR Controls Acetate Assimilation by Directly Repressing the acsA Gene in Saccharopolyspora erythraea

Abstract

The GntR family regulator DasR controls the transcription of genes involved in chitin and N-acetylglucosamine (GlcNAc) metabolism in actinobacteria. GlcNAc is catabolized to ammonia, fructose-6-phosphate (Fru-6P), and acetate, which are nitrogen and carbon sources. In this work, a DasR-responsive element (dre) was observed in the upstream region of acsA1 in Saccharopolyspora erythraea This gene encodes acetyl coenzyme A (acetyl-CoA) synthetase (Acs), an enzyme that catalyzes the conversion of acetate into acetyl-CoA. We found that DasR repressed the transcription of acsA1 in response to carbon availability, especially with GlcNAc. Growth inhibition was observed in a dasR-deleted mutant (ΔdasR) in the presence of GlcNAc in minimal medium containing 10 mM acetate, a condition under which Acs activity is critical to growth. These results demonstrate that DasR controls acetate assimilation by directly repressing the transcription of the acsA1 gene and performs regulatory roles in the production of intracellular acetyl-CoA in response to GlcNAc.IMPORTANCE Our work has identified the DasR GlcNAc-sensing regulator that represses the generation of acetyl-CoA by controlling the expression of acetyl-CoA synthetase, an enzyme responsible for acetate assimilation in S. erythraea The finding provides the first insights into the importance of DasR in the regulation of acetate metabolism, which encompasses the regulatory network between nitrogen and carbon metabolism in actinobacteria, in response to environmental changes.

Keywords: GntR family regulator DasR; acetate assimilation; acetyl-CoA synthetase; acetylglucosamine metabolism.