Nudix hydrolases with Coenzyme A (CoA) and acyl-CoA pyrophosphatase activities confer growth advantage to Mycobacterium smegmatis

Kapoor, Indu and Varada, Rajagopal and Aroli, Shashanka and Varshney, Umesh (2019) Nudix hydrolases with Coenzyme A (CoA) and acyl-CoA pyrophosphatase activities confer growth advantage to Mycobacterium smegmatis. In: MICROBIOLOGY-SGM, 165 (11). pp. 1219-1232.

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Abstract

Nudix hydrolase family proteins hydrolyse toxic by-products of cellular metabolism such as mutagenic nucleoside triphosphates, sugar nucleotides and signalling molecules. We studied the substrate specificities of Nudix hydrolases encoded by rv3672c and rv3040c from Mycobacterium tuberculosis and their respective homologues, msmeg_6185 and msmeg_2327 from M. smegmatis. The rv3672c- and msmeg_6185-encoded proteins (Rv3672 and MSMEG_6185, respectively) showed CoA pyrophosphatase (CoAse) activity that converted acyl-CoA to adenosine-3',5'-diphosphate (3', 5'-ADP) and 4-acyl phosphopantetheine. The efficiencies of Rv3672 and MSMEG_6185 in hydrolysing CoA derivatives were found to be higher than those of the Rv3040 and MSMEG_2327 (encoded by rv3040c and msmeg_2327, respectively). Further, amongst the substrates tested, Rv3672 and MSMEG_6185 used CoA and oxidized CoA as the most preferred substrates. Use of the M. smegmatis model showed that the expression of msmeg_6185 occurs in the log and stationary phases but declines during the late stationary phase and becomes undetectable during hypoxia. The co-culture competition experiments performed between the wild-type and Delta msmeg_6185 strains of M. smegmatis in different carbon sources revealed that the presence of msmeg_6185 provided growth fitness advantage to M. smegmatis, irrespective of the carbon source, implicating its function in regulation for the optimal physiological levels of acyl-CoAs in the cell.

Item Type:	Journal Article
Publication:	MICROBIOLOGY-SGM
Publisher:	MICROBIOLOGY SOC
Additional Information:	Copyright of this article belongs to MICROBIOLOGY SOC
Keywords:	Nudix hydrolase; Coenzyme A pyrophosphatase; Mycobacterium smegmatis; rv3672c; rv3040c; msmeg_6185 and msmeg_2327
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	17 Dec 2019 09:55
Last Modified:	17 Dec 2019 09:55
URI:	http://eprints.iisc.ac.in/id/eprint/63945

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