ModE-dependent molybdate regulation of the molybdenum cofactor operon moa in Escherichia coli

The expression of the moa locus, which encodes enzymes required for molybdo pterin biosynthesis, is enhanced under anaerobiosis but repressed when the bacterium is able to synthesize active molybdenum cofactor. In addition, mo a expression exhibits a strong requirement for molybdate. The molybdate enh ancement of moa transcription is fully dependent upon the molybdate-binding protein, ModE, which also mediates molybdate repression of the mod operon encoding the high-affinity molybdate uptake system. Due to the repression o f moa in molybdenum cofactor-sufficient strains, the positive molybdate reg ulation of moa is revealed only in strains unable to make the active cofact or. Transcription of moa is controlled at two sigma-70-type promoters immed iately upstream of the moaA gene. Deletion mutations covering the region up stream of moaA have allowed each of the promoters to be studied in isolatio n. The distal promoter is the site of the anaerobic enhancement which is Fn r-dependent. The molybdate induction of moa is exerted at the proximal prom oter. Molybdate-ModE binds adjacent to the -35 region of this promoter, act ing as a direct positive regulator of moa. The molybdenum cofactor repressi on also appears to act at the proximal transcriptional start site, but the mechanism remains to be established. Tungstate in the growth medium affects moa expression in two ways. Firstly, it can act as a functional molybdate analogue for the ModE-mediated regulation. Secondly, tungstate brings about the loss of the molybdenum cofactor repression of moa, It is proposed that the tungsten derivative of the molybdenum cofactor, which is known to be f ormed under such conditions, is ineffective in bringing about repression of moa. The complex control of moa is discussed in relation to the synthesis of molybdoenzymes in the bacterium.