Cyclic AMP-dependent protein lysine acylation in mycobacteria regulates fatty acid and propionate metabolism

Nambi, Subhalaxmi and Gupta, Kallol and Bhattacharyya, Moitrayee and Ramakrishnan, Parvathy and Ravikumar, Vaishnavi and Siddiqui, Nida and Thomas, Ann Terene and Visweswariah, Sandhya S (2013) Cyclic AMP-dependent protein lysine acylation in mycobacteria regulates fatty acid and propionate metabolism. In: Journal Of Biological Chemistry, 288 (20). pp. 14114-14124.

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Abstract

Acetylation of lysine residues is a posttranslational modification that is used by both eukaryotes and prokaryotes to regulate a variety of biological processes. Here we identify multiple substrates for the cAMP-dependent protein lysine acetyltransferase from Mycobacterium tuberculosis (KATmt). We demonstrate that a catalytically important lysine residue in a number of FadD (fatty acyl CoA synthetase) enzymes is acetylated by KATmt in a cAMP-dependent manner and that acetylation inhibits the activity of FadD enzymes. A sirtuin-like enzyme can deacetylate multiple FadDs, thus completing the regulatory cycle. Using a strain deleted for the KATmt ortholog in Mycobacterium bovis Bacillus Calmette-Guerin (BCG), we show for the first time that acetylation is dependent on intracellular cAMP levels. KATmt can utilize propionyl CoA as a substrate and, therefore, plays a critical role in alleviating propionyl CoA toxicity in mycobacteria by inactivating acyl CoA synthetase (ACS). The precision by which mycobacteria can regulate the metabolism of fatty acids in a cAMP-dependent manner appears to be unparalleled in other biological organisms and is ideally suited to adapt to the complex environment that pathogenic mycobacteria experience in the host.

Item Type:	Journal Article
Publication:	Journal Of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology, Inc
Additional Information:	Copyright of this article belongs to American Society for Biochemistry and Molecular Biology, Inc.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	11 Jul 2013 06:25
Last Modified:	11 Jul 2013 06:25
URI:	http://eprints.iisc.ac.in/id/eprint/46818

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