Biosynthesis of sulfated glycopeptide antibiotics by using the sulfotransferase StaL.
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.
Lamb
Sherry S
SS
Antimicrobial Research Centre, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Patel
Tejal
T
Koteva
Kalinka P
KP
Wright
Gerard D
GD
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001483:Base Sequence; D015139:Blotting, Southern; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D006020:Glycopeptides / Q000737:chemistry*; D013302:Streptomyces / Q000201:enzymology / Q000378:metabolism; D013431:Sulfates / Q000737:chemistry*; D015238:Sulfotransferases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D017931:DNA Primers; D006020:Glycopeptides; D013431:Sulfates; D015238:Sulfotransferases