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Biosynthesis of sulfated glycopeptide antibiotics by using the sulfotransferase StaL.
Lamb, Sherry S; Patel, Tejal; Koteva, Kalinka P; Wright, Gerard D.
Afiliación
  • Lamb SS; Antimicrobial Research Centre, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Chem Biol ; 13(2): 171-81, 2006 Feb.
Article en En | MEDLINE | ID: mdl-16492565
The unique glycopeptide antibiotic A47934, produced by Streptomyces toyocaensis, possesses a nonglycosylated heptapeptide core that is sulfated on the phenolic hydroxyl of the N-terminal 4-hydroxy-L-phenylglycine residue. Genetic and biochemical experiments confirmed that StaL is a sulfotransferase capable of sulfating the predicted crosslinked heptapeptide substrate to produce A47934 both in vivo and in vitro. Incubation of purified His(6)-StaL with various substrates in vitro revealed substrate specificity and yielded two sulfo-glycopeptide antibiotics: sulfo-teicoplanin aglycone and sulfo-teicoplanin. Quantification of the antibacterial activity of desulfo-A47934, A47934, teicoplanin, and sulfo-teicoplanin demonstrated that sulfation slightly increased the minimum inhibitory concentration. This unique modification by sulfation expands glycopeptide diversity with potential application for the development of new antibiotics.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfatos / Glicopéptidos / Sulfotransferasas / Antibacterianos Idioma: En Revista: Chem Biol Asunto de la revista: BIOLOGIA / BIOQUIMICA / QUIMICA Año: 2006 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfatos / Glicopéptidos / Sulfotransferasas / Antibacterianos Idioma: En Revista: Chem Biol Asunto de la revista: BIOLOGIA / BIOQUIMICA / QUIMICA Año: 2006 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos