Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli

The suppressor mutation, named sfhC21, that allows Escherichia coil ftsH nu ll mutant cells to survive was found to be an allele of fabZ encoding R-3-h ydroxyacyl-ACP dehydrase, involved in a key step of fatty acid biosynthesis , and appears to upregulate the dehydrase. The ffsH1(Ts) mutation increased the amount of lipopolysaccharide at 42 degrees C. This was accompanied by a dramatic increase in the amount of UDP-3-O-(R-3-hydroxymyristoyl)-N-acety lglucosamine deacetylase [the IpxC (envA) gene product] involved in the com mitted step of lipid A biosynthesis. Pulse-chase experiments and in vitro a ssays with purified components showed that FtsH, the AAA-type membrane-boun d metalloprotease, degrades the deacetylase. Genetic evidence also indicate d that the FtsH protease activity for the deacetylase might be affected whe n acyl-ACP pools were altered. The biosynthesis of phospholipids and the li pid A moiety of lipopolysaccharide, both of which derive their fatty acyl c hains from the same R-3-hydroxyacyl-ACP pool, is regulated by FtsH.