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.
Antimicrobial Research Centre, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Sherry S
SS
Lamb
Tejal
T
Patel
Kalinka P
KP
Koteva
Gerard D
GD
Wright
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