Artículo
Revisiting the coupling of fatty acid to phospholipid synthesis in bacteria with FapR regulation
Machinandiarena, Federico
; Nakamatsu, Leandro; Schujman, Gustavo Enrique
; de Mendoza, Diego
; Albanesi, Daniela
Fecha de publicación:
07/2020
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
Molecular Microbiology
ISSN:
0950-382X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
A key aspect in membrane biogenesis is the coordination of fatty acid to phospholipid synthesis rates. In most bacteria, PlsX is the first enzyme of the phosphatidic acid synthesis pathway, the common precursor of all phospholipids. Previously, we proposed that PlsX is a key regulatory point that synchronizes the fatty acid synthase II with phospholipid synthesis in Bacillus subtilis. However, understanding the basis of such coordination mechanism remained a challenge in Gram-positive bacteria. Here, we show that the inhibition of fatty acid and phospholipid synthesis caused by PlsX depletion leads to the accumulation of long-chain acyl-ACPs, the end products of the fatty acid synthase II. Hydrolysis of the acyl-ACP pool by heterologous expression of a cytosolic thioesterase relieves the inhibition of fatty acid synthesis, indicating that acyl-ACPs are feedback inhibitors of this metabolic route. Unexpectedly, inactivation of PlsX triggers a large increase of malonyl-CoA leading to induction of the fap regulon. This finding discards the hypothesis, proposed for B. subtilis and extended to other Gram-positive bacteria, that acyl-ACPs are feedback inhibitors of the acetyl-CoA carboxylase. Finally, we propose that the continuous production of malonyl-CoA during phospholipid synthesis inhibition provides an additional mechanism for fine-tuning the coupling between phospholipid and fatty acid production in bacteria with FapR regulation.
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Articulos(IBR)
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Citación
Machinandiarena, Federico; Nakamatsu, Leandro; Schujman, Gustavo Enrique; de Mendoza, Diego; Albanesi, Daniela; Revisiting the coupling of fatty acid to phospholipid synthesis in bacteria with FapR regulation; Wiley Blackwell Publishing, Inc; Molecular Microbiology; 114; 4; 7-2020; 653-663
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