title: Towards structural determination of the ComX pheromone: synthetic studies on peptides containing geranyltryptophan.
abstract: Bacteria produce and respond to signal molecules depending on their cell density. This process is called "quorum sensing". The ComX pheromone, controlled by quorum sensing, activates natural genetic competence in Bacillus subtilis. ComX is an oligopeptide with a posttranslational modification. It has been suggested that ComX pheromone is modified with an isoprenoid at its tryptophan residue, but the complete chemical structure is unknown. We first determined the molecular formula of ComX(RO-E-2), a competence factor for B. subtilis strain RO-E-2. Then we synthesized putative pheromones with 1-, 2-, 4-, 5-, 6-, or 7-geranyl substituted tryptophan residues. The regio- and stereo-selective synthesis of the geranyl tryptophans was successful, and we prepared the six peptides with modified tryptophan residues. These peptides had the same molecular formula and showed similar hydrophobicity to the natural ComX(RO-E-2) in LC-MS analysis. But, none of them showed the same retention time as the natural pheromone and none exhibited its biological activity. These results suggest that the isoprenoid modification pattern of the tryptophan residue is more complex than postulated.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.forename: Isao
authors.initials: I
authors.lastname: Sato
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Cho
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
authors.forename: David
authors.initials: D
authors.lastname: Dubnau
authors.forename: Youji
authors.initials: Y
authors.lastname: Sakagami
mesh_terms: D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004926:Escherichia coli / Q000378:metabolism; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis*; D010675:Pheromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C087040:ComX protein, Bacillus subtilis; D007202:Indicators and Reagents; D010455:Peptides; D010675:Pheromones; D014364:Tryptophan