The molecular basis for positive regulation of cys promoters in Salmonella typhimurium and Escherichia coli

Abstract

Most genes required for cysteine biosynthesis in Salmonella typhimurium and Escherichia coli are positively regulated by cysB, which encodes a transcriptional activator belonging to the LysR family of regulatory proteins. CysB protein binds just upstream of the -35 region of positively regulated promoters, where in the presence of inducer it facilitates formation of a transcription initiation complex. CysB protein also autoregulates its own synthesis by binding to the cysB promoter as a repressor. Cysteine down-regulates the pathway by inhibiting synthesis of O-acetylserine, a direct cysteine precursor and possibly an inducer of gene expression. O-Acetylserine spontaneously isomerizes to N-acetylserine, which is clearly an inducer. Sulphide and thiosulphate provide additional regulation by acting as anti-inducers. Inducer stimulates CysB protein binding to sites involved in positive regulation, and inhibits binding to the negatively autoregulated cysB promoter. For three sites with unknown function, binding is stimulated at one and inhibited at the other two.