Guanosine tetraphosphate inhibition of fatty acid and phospholipid synthesis in Escherichia coli is relieved by overexpression of glycerol-3-phosphate acyltransferase (plsB).
The accumulation of the alarmone guanosine-3',5'-bispyrophosphate (ppGpp) in response to amino acid starvation or energy source depletion mediates the coordinate inhibition of macromolecular and membrane phospholipid biosynthesis in Escherichia coli. Accumulation of ppGpp triggered by the induced expression of either the relA gene or an unregulated, truncated relA gene that encodes a constitutively active ppGpp synthetase I, inhibited both de novo fatty acid and phospholipid biosynthesis and the incorporation of exogenous fatty acids into phospholipid. ppGpp inhibition of fatty acid and phospholipid synthesis was associated with an accumulation of long-chain acyl-ACP, the end products of fatty acid biosynthesis, and substrates for the sn-glycerol-3-phosphate acyltransferase (the plsB gene product). Overexpression of the plsB gene product relieved the inhibition of fatty acid and phospholipid synthesis, prevented the accumulation of long-chain acyl-ACPs, and allowed an increase in cell size following elevation of intracellular ppGpp. However, stable RNA accumulation and cell division were still blocked by ppGpp accumulation. These data show that the sn-glycerol-3-phosphate acyltransferase mediates the ppGpp-dependent regulation of fatty acid and phospholipid biosynthesis in E. coli.
Heath
R J
RJ
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Jackowski
S
S
Rock
C O
CO
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000213:Acyl Carrier Protein / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000502:physiology*; D006159:Guanosine Tetraphosphate / Q000494:pharmacology; D010743:Phospholipids / Q000096:biosynthesis*
D000085:Acetates; D000213:Acyl Carrier Protein; D005227:Fatty Acids; D010743:Phospholipids; D006159:Guanosine Tetraphosphate; D005992:Glycerol-3-Phosphate O-Acyltransferase; D019342:Acetic Acid