Jin Jin, Huan Chen, Ning Wang, Kemeng Zhu, Huanhuan Liu, Dongfang Shi, Jiuqing Xin, Henggui Liu

Front Microbiol.2021 Jan 18;11:631433.doi: 10.3389/fmicb.2020.631433. eCollection 2020

Abstract

Lipoic acid is a conserved cofactor necessary for the activation of several critical enzyme complexes in the aerobic metabolism of 2-oxoacids and one-carbon metabolism. Lipoate metabolism enzymes are key for lipoic acid biosynthesis and salvage. In this study, we found that Mycoplasma hyopneumoniae (M. hyopneumoniae) Mhp-Lpl, which had been previously shown to have lipoate-protein ligase activity against glycine cleavage system H protein (GcvH) in vitro, did not lipoylate the lipoate-dependent subunit of dihydrolipoamide dehydrogenase (PdhD). Further studies indicated that a new putative lipoate-protein ligase in M. hyopneumoniae, MHP_RS00640 (Mhp-LplJ), catalyzes free lipoic acid attachment to PdhD in vitro. In a model organism, Mhp-LplJ exhibited lipoate and octanoate ligase activities against PdhD. When the enzyme activity of Mhp-LplJ was disrupted by lipoic acid analogs, 8-bromooctanoic acid (8-BrO) and 6,8-dichlorooctanoate (6,8-diClO), M. hyopneumoniae growth was arrested in vitro. Taken together, these results indicate that Mhp-LplJ plays a vital role in lipoic acid metabolism of M. hyopneumoniae, which is of great significance to further understand the metabolism of M. hyopneumoniae and develop new antimicrobials against it.

Keywords: Mycoplasma hyopneumoniae; dihydrolipoamide dehydrogenase; lipoate-protein ligase; lipoic acid; lipoic acid analogs.

Copyright © 2021 Jin, Chen, Wang, Zhu, Liu, Shi, Xin and Liu.