A lipA (yutB) mutant, encoding lipoic acid synthase, provides insight into the interplay between branched-chain and unsaturated fatty acid biosynthesis in Bacillus subtilis.

MARTIN, N; LOMBARDÍA, E; ALTABE, SG; DE MENDOZA, D; MANSILLA, MC

JOURNAL OF BACTERIOLOGY

American Society of Microbiology

Año: 2009 vol. 191 p. 7447 - 7455

0021-9193

Lipoic acid is an essential cofactor required for the function of key metabolic pathways in most organisms. We report the characterization of a Bacillus subtilis mutant obtained by disruption of the lipA (yutB) gene which encodes the enzyme lipoyl synthase (LipA) that catalyzes the final step in the de novo biosynthesis of this cofactor. The function of lipA was inferred from genetic and physiological experiments and this study investigated its role in B. subtilis fatty acid metabolism. Interrupting lipoate-dependent reactions strongly inhibits growth in minimal media, impairing the generation of branched chain fatty acids and leading to accumulation of copious amounts of straight-chain saturated fatty acids into B. subtilis membranes. Although depletion of LipA induces the expression of the Delta5-desaturase, controlled by a two-component system that senses changes in membrane properties, the synthesis of unsaturated fatty acids is insufficient to support growth in the absence of precursors for branched chain fatty acids. However, deregulated overexpression of the Delta5-desaturase functionally replaces the deficiency of lipoic acid-dependent synthesis of branched-chain fatty acids. Furthermore, we show that the cold-sensitive phenotype of a B. subtilis strain deficient in Delta5-desaturase is suppressed by isoleucine only if LipA is present.