The McbR repressor modulated by the effector substance S-adenosylhomocysteine controls directly the transcription of a regulon involved in sulphur metabolism of Corynebacterium glutamicum ATCC 13032

In a recent proteomics study we have shown that the mcbR gene of Corynebacterium glutamicum ATCC 13032 most probably encodes a transcriptional repressor of the TetR type, which regulates the expression of at least six genes involved in the synthesis of sulphur-containing amino acids. By means of DNA microarray hybridizations we detected 86 genes with enhanced transcription in an mcbR mutant when compared with the wild-type strain. Bioinformatic analysis identified the inverted repeat 5'-TAGAC-N6-GTCTA-3' as a consensus sequence within the upstream region of 22 genes and operons, suggesting that the transcription of at least 45 genes is directly controlled by the McbR repressor. These 45 genes encode a variety of functions in (S-adenosyl)methionine and cysteine biosynthesis, in sulphate reduction, in uptake and utilization of sulphur-containing compounds and in transcriptional regulation. The function of the inverted repeat motif as potential McbR binding site in front of the genes hom, cysI, cysK, metK and mcbR was verified experimentally by competitive electrophoretic mobility shift analysis. A systematic search for the potential effector substance modulating the function of McbR revealed that only S-adenosylhomocysteine prevented the binding of McbR to its target sequence. These results indicate that the transcriptional repressor McbR directly regulates a set of genes comprising all aspects of transport and metabolism of the macroelement sulphur in C. glutamicum. As the activity of McbR is modulated by S-adenosylhomocysteine, a major product of transmethylation reactions, the results point also to a novel regulatory mechanism in bacteria to control the biosynthesis of S-adenosylmethionine.