Acetylation Coordinates the Crosstalk between Carbon Metabolism and Ammonium Assimilation

ABSTRACT: Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH), in response to low or high ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation are not fully elucidated. Here, we report that, in Salmonella, carbon metabolism coordinates the activities of GS/GDH via functional reversible protein lysine acetylation. Glucose simultaneously promotes acetyltransferase Pat-mediated acetylation on Lys164 and Lys353 of GS to activate the adenylylated-GS by inducing its conformation change, while on Lys128 of GDH to inactivate the enzyme by impeding its catalytic center, respectively, which are reversed by deacetylase CobB-mediated deacetylation. Molecular dynamic (MD) simulations indicated that the acetylation activation of GS activity was adenylylation-dependent. Acetylation and deacetylation occur within minutes of ‘glucose shock’ to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Acetylation can rehabilitate the growth tardiness of Salmonella mutant with chromosomal mimetic mutation of adenylylated-GS and thus help its survival in mice. Thus, glucose-driven acetylation integrates the signals of assimilation and carbon metabolism for proper growth control.

INSTRUMENT(S):

ORGANISM(S): Salmonella Typhimurium (strain Lt2 / Sgsc1412 / Atcc 700720)

SUBMITTER: Qijun Wang  

LAB HEAD: Qijun Wang

PROVIDER: PXD039658 | Pride | 2023-06-21

REPOSITORIES: Pride