Control of membrane lipid homeostasis in bacteria

ALBANESI, DANIELA; MACHINANDIARENA, FEDERICO; DE MENDOZA, DIEGO

Paraná, Entre Ríos, Argentina

Congreso; LIV Congreso de la Sociedad Argentina de Investigación Bioquímica (SAIB).; 2018

SAIB

Bacteria strictly control the synthesis of their membrane phospholipids in response to different nutritional conditions but the underlying regulatory mechanisms are obscure. In Bacillus subtilis fatty acids (FA) are produced by a type II synthase (FASII) consisting of a repeated cycle of reactions. In FASII, all fatty acyl intermediates are covalently linked to acyl carrier protein (ACP) and shuttled from one enzyme to another. Malonyl-CoA, which is synthesized by acetyl-CoA carboxylase (ACC), is an essential lipid intermediate in FA biosynthesis in all living cells. When the acyl-ACPs reach the proper length, they become substrates for the enzymes involved in phospholipid synthesis (PLS): PlsX (acyl-ACP:PO4 acyltransferase), PlsY (acyl-PO4:glycerol-PO4 acyltransferase) and PlsC (acyl-ACP:1-acylglycerol-PO4 acyltransferase). In our lab, it was shown that FASII and PLS are coupled at the PlsX step in B. subtilis. In the absence of PlsX, both PLS and FA synthesis are arrested. Here, we show that a ΔplsX strain accumulates acyl-ACPs and malonyl-CoA, indicating that ACC activity is not repressed. Moreover, acyl-ACPs hydrolysis by heterologous expression of a thioesterase (TesA) does not fully release inhibition of FASII in a plsX mutant. Furthermore, we determined that plsY and plsC mutants also accumulate high levels of long chain acyl-ACPs while exhibiting an active FASII. These findings suggest that in B. subtilis, in contrast to other bacteria, long chain acyl-ACPs are not feedback inhibitors of ACC and FASII. Our results shed new light into the control of lipid homeostasis in bacteria