The periplasmic dipeptide permease system transports 5-aminolevulinic acid in Escherichia coli.

In a genetic screen designed to generate Escherichia coli strains completely devoid of the heme precursor 5-aminolevulinic acid (ALA), we isolated a class of mutants which were defective for exogenous ALA uptake. The mutations, designated alu (ALA uptake), mapped to the 80-min region of the E. coli chromosome. They were complemented by a recombinant plasmid containing the dpp operon, which encodes a dipeptide permease transport system. Alu mutants displayed a severe reduction in ALA import, as did a strain with a chromosomal insertion in the first gene of the dpp operon. A recognized substrate of Dpp transport, prolyl-glycine, effectively competed with ALA for uptake. E. coli strains defective in ALA biosynthesis (hemA or hemL) require exogenous ALA to achieve wild-type growth but show limited aerobic and anaerobic growth in the absence of ALA. The presence of an alu or dpp mutation in hemA or hemL strains abolishes growth in the absence of ALA and requires increased levels of ALA for normal growth. We conclude that the alu mutations are within the dpp operon and that the dipeptide transport system mediates uptake of the important metabolite ALA.