Unravelling the lipoyl‐relay of exogenous lipoate utilization in Bacillus subtilis

MARTIN, N; RASETTO, N; MANSILLA, MC; LAVATELLI, A

MOLECULAR MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2019 vol. 112 p. 302 - 316

0950-382X

Lipoate is anessential cofactor for key enzymes of oxidative and one-carbon metabolism. Itis covalently attached to E2 subunits of dehydrogenase complexes and GcvH, the Hsubunit of the glycine cleavage system. Bacillussubtilis possess two protein lipoylation pathways: biosynthesis andscavenging. The former requires octanoylation of GcvH, insertion of sulfuratoms and amidotransfer of the lipoate to E2s, catalyzed by LipL. Lipoate scavengingis mediated by a lipoyl protein ligase (LplJ) that catalyzes a classical two-stepATP-dependent reaction. Although these pathways were thought to be redundant, a∆lipL mutant, in which the endogenouslipoylation pathway of E2 subunits is blocked, showed growth defects in minimalmedia even when supplemented with lipoate, and despite the presence of afunctional LplJ. In this study we demonstrate that LipL is essential to modifyE2 subunits of branched chain ketoacid and pyruvate dehydrogenases during lipoatescavenging. The crucial role of LipL during lipoate utilization relies on thestrict substrate specificity of LplJ, determined by charge complementaritybetween the ligase and the lipoylable subunits. This new lipoyl-relay requiredfor lipoate scavenging highlights the relevance of the amidotransferase as avalid target for the design of new antimicrobial agents among Gram-positivepathogens.