A new pathway for the synthesis of alpha-ribazole-phosphate in Listeria innocua

作者：Gray Michael J; Escalante Semerena Jorge C^*

来源：Molecular Microbiology, 2010, 77(6): 1429-1438.

DOI：10.1111/j.1365-2958.2010.07294.x

P>The genomes of Listeria spp. encode all but one of 25 enzymes required for the biosynthesis of adenosylcobalamin (AdoCbl; coenzyme B(12)). Notably, all Listeria genomes lack CobT, the nicotinamide mononucleotide:5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (EC 2.4.2.21) enzyme that synthesizes the unique alpha-linked nucleotide N1-(5-phospho-alpha-d-ribosyl)-DMB (alpha-ribazole-5'-P, alpha-RP), a precursor of AdoCbl. We have uncovered a new pathway for the synthesis of alpha-RP in Listeria innocua that circumvents the lack of CobT. The cblT and cblS genes (locus tags lin1153 and lin1110) of L. innocua encode an alpha-ribazole (alpha-R) transporter and an alpha-R kinase respectively. Results from in vivo experiments indicate that L. innocua depends on CblT and CblS activities to salvage exogenous alpha-R, allowing conversion of the incomplete corrinoid cobinamide (Cbi) into AdoCbl. Expression of the L. innocua cblT and cblS genes restored AdoCbl synthesis from Cbi and alpha-R in a Salmonella enterica cobT strain. LinCblT transported alpha-R across the cell membrane, but not alpha-RP or DMB. UV-visible spectroscopy and mass spectrometry data identified alpha-RP as the product of the ATP-dependent alpha-R kinase activity of LinCblS. Bioinformatics analyses suggest that alpha-R salvaging occurs in important Gram-positive human pathogens.

• 出版日期2010-9