[MINIREVIEW] Alanine dehydrogenases in mycobacteria

Ji-A Jeong; Jeong-Il Oh

doi:10.1007/s12275-019-8543-7

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[MINIREVIEW] Alanine dehydrogenases in mycobacteria: Ji-A Jeong , Jeong-Il Oh; Journal of Microbiology 2019;57(2):81-92.
DOI: https://doi.org/10.1007/s12275-019-8543-7
Published online: January 31, 2019

Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of KoreaDepartment of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea

Corresponding author: Jeong-Il Oh , Tel: +82-51-510-2593;,

Received: 8 September 2018 • Revised: 31 October 2018 • Accepted: 7 November 2018

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Abstract

Since NAD(H)-dependent L-alanine dehydrogenase (EC 1.1.4.1; Ald) was identified as one of the major antigens present in culture filtrates of Mycobacterium tuberculosis, many studies on the enzyme have been conducted. Ald catalyzes the reversible conversion of pyruvate to alanine with concomitant oxidation of NADH to NAD+ and has a homohexameric quaternary structure. Expression of the ald genes was observed to be strongly upregulated in M. tuberculosis and Mycobacterium smegmatis grown in the presence of alanine. Furthermore, expression of the ald genes in some mycobacteria was observed to increase under respiration-inhibitory conditions such as oxygen-limiting and nutrient-starvation conditions. Upregulation of ald expression by alanine or under respiration-inhibitory conditions is mediated by AldR, a member of the Lrp/AsnC family of transcriptional regulators. Mycobacterial Alds were demonstrated to be the enzymes required for utilization of alanine as a nitrogen source and to help mycobacteria survive under respiration-inhibitory conditions by maintaining cellular NADH/NAD+ homeostasis. Several inhibitors of Ald have been developed, and their application in combination with respiration-inhibitory antitubercular drugs such as Q203 and bedaquiline was recently suggested.

Keywords: alanine dehydrogenase;gene regulation;Lrp/AsnC family regulator;mycobacteria;redox homeostasis

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[MINIREVIEW] Alanine dehydrogenases in mycobacteria

J. Microbiol. 2019;57(2):81-92. Published online January 31, 2019

DOI: https://doi.org/10.1007/s12275-019-8543-7

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