title: Synthesis of bacillithiol and the catalytic selectivity of FosB-type fosfomycin resistance proteins.
abstract: Bacillithiol (BSH) has been prepared on the gram scale from the inexpensive starting material, D-glucosamine hydrochloride, in 11 steps and 8-9% overall yield. The BSH was used to survey the substrate and metal-ion selectivity of FosB enzymes from four Gram-positive microorganisms associated with the deactivation of the antibiotic fosfomycin. The in vitro results indicate that the preferred thiol substrate and metal ion for the FosB from Staphylococcus aureus are BSH and Ni(II), respectively. However, the metal-ion selectivity is less distinct with FosB from Bacillus subtilis, Bacillus anthracis, or Bacillus cereus.
authors.affiliation: Department of Chemistry, Vanderbilt University, Vanderbilt Institute of Chemical Biology, Nashville, Tennessee 37235, USA.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Lamers
authors.forename: Mary E
authors.initials: ME
authors.lastname: Keithly
authors.forename: Kwangho
authors.initials: K
authors.lastname: Kim
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cook
authors.forename: Donald F
authors.initials: DF
authors.lastname: Stec
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Hines
authors.forename: Gary A
authors.initials: GA
authors.lastname: Sulikowski
authors.forename: Richard N
authors.initials: RN
authors.lastname: Armstrong
mesh_terms: D001407:Bacillus / Q000378:metabolism; D055162:Biocatalysis; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005578:Fosfomycin / Q000737:chemistry / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D015394:Molecular Structure; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D016760:Proto-Oncogene Proteins c-fos; C543521:bacillithiol; D005578:Fosfomycin; D003545:Cysteine; D005944:Glucosamine