Acetyl‐CoA synthetases of Saccharopolyspora erythraea are regulated by the nitrogen response regulator GlnR at both transcriptional and post‐translational levels. Issue 5 (23rd January 2017)

• Record Type: Journal Article
• Authors: You, Di; Wang, Miao‐Miao; Ye, Bang‐Ce
• Is Part Of: Molecular microbiology. Volume 103:Issue 5(2017)
• Page Start: 845
• Page End: 859
• Publication Date: 2017-01-23
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13595
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: Saccharopolyspora erythraea has three AMP‐forming acetyl‐CoA synthetases (Acs) encoded by acsA1, acsA2, and acsA3 . In this work, we found that nitrogen response regulator GlnR can directly interact with the promoter regions of all three genes and can activate their transcription in response to nitrogen availability. The typical GlnR‐binding boxes were identified in the promoter regions. Moreover, the activities of three Acs enzymes were modulated by the reversible lysine acetylation (RLA) with acetyltransferase AcuA and NAD + ‐dependent deacetylase SrtN. Interestingly, GlnR controlled the RLA by directly activating the expression of acuA and srtN . A glnR ‐deleted mutant (Δ glnR ) caused a growth defect in 10 mM acetate minimal medium, a condition under which RLA function is critical to control Acs activity. Overexpression of acuA reversed the growth defect of Δ glnR mutant. Total activity of Acs in cell‐free extracts from Δ glnR strain had a 4‐fold increase relative to that of wildtype strain. Western Blotting showed that in vivo acetylation levels of Acs were influenced by nitrogen availability and lack of glnR . These results demonstrated that GlnR regulated acetyl‐CoA synthetases at transcriptional and post‐translational levels, and mediated the interplay between nitrogen and carbon metabolisms by integrating nitrogen signals to modulate the acetate metabolism. Abstract : Nitrogen‐sensing pleiotropic regulator GlnR directly controls acetate assimilation at the transcriptional and post‐translational levels. This finding provides the first insights into the integration of nitrogen metabolism, acetate metabolism, and protein lysine acetylation system to construct a regulatory network controlling nitrogen/carbon metabolism in response to the environmental changes.