title: ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster.
abstract: Multidrug transporters play key roles in cellular drug resistance to toxic molecules, yet these transporters are also involved in natural product transport as part of biosynthetic clusters in bacteria and fungi. The genotoxic molecule colibactin is produced by strains of virulent and pathobiont Escherichia coli and Klebsiella pneumoniae. In the biosynthetic cluster is a multidrug and toxic compound extrusion protein (MATE) proposed to transport the prodrug molecule precolibactin across the cytoplasmic membrane, for subsequent cleavage by the peptidase ClbP and cellular export. We recently determined the X-ray structure of ClbM, and showed preliminary data suggesting its specific role in precolibactin transport. Here, we define a functional role of ClbM by examining transport capabilities under various biochemical conditions. Our data indicate ClbM responds to sodium, potassium, and rubidium ion gradients, while also having substantial transport activity in the absence of alkali cations.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: Jarrod J
authors.initials: JJ
authors.lastname: Mousa
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Newsome
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA. Electronic address: bruner@ufl.edu.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bruner
mesh_terms: D017920:Antiporters / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry; D001692:Biological Transport; D001693:Biological Transport, Active; D002412:Cations; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D007711:Klebsiella pneumoniae / Q000378:metabolism; D064307:Microbiota; D005810:Multigene Family; D009154:Mutation; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*; D011188:Potassium / Q000737:chemistry; D011355:Prodrugs; D017433:Protein Structure, Secondary; D012235:Rhodamines / Q000737:chemistry; D012413:Rubidium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D001688:Biological Products; D002412:Cations; C000619950:ClbM protein, E coli; D029968:Escherichia coli Proteins; D027701:Organic Cation Transport Proteins; D010455:Peptides; D061065:Polyketides; D011355:Prodrugs; D012235:Rhodamines; C569566:colibactin; C026188:rhodamine 6G; D014867:Water; D012964:Sodium; C577770:ClbP protein, E coli; D010447:Peptide Hydrolases; D012413:Rubidium; D011188:Potassium
keywords: Drug biosynthesis; Microbiome; Multidrug transporter; Natural product