Biosynthesis of sulfated glycopeptide antibiotics by using the sulfotransferase StaL |
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Authors: | Lamb Sherry S Patel Tejal Koteva Kalinka P Wright Gerard D |
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Affiliation: | Antimicrobial Research Centre, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. |
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Abstract: | 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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