Proline excretion and indirect suppression in Escherichia coli and Salmonella typhimurium

The last step in proline biosynthesis in Escherichia coli K-12, Salmonella typhimurium LT7, and a number of other enterobacterial isolates is regulated so that no proline is excreted, even if excess Delta(1)-pyrroline-5-carboxylate, the immediate precursor of proline, is added to a culture. In proline auxotrophs blocked at an early step in proline biosynthesis (proA or proB), reversion to prototrophy is often due to a mutation in the arginine pathway which diverts N-acetyl glutamate gamma-semialdehyde to proline synthesis, thus bypassing the proA or proB block. In such double mutants (proAB, argD), the last step in proline synthesis appears to be unregulated, since proline is excreted. Feedback inhibition and repression of the arginine pathway overcomes indirect suppression (restoring the Pro(-) phenotype), but proline regulation is not restored; double mutants still excrete proline when fed Delta(1)-pyrroline-5-carboxylate exogeneously. A new class of proline analogue-resistant mutant, due to mutation at argD, is also described.