title: Studies on the formation and incorporation of streptolidine in the biosynthesis of the peptidyl nucleoside antibiotic streptothricin F.
abstract: Streptothricin F (STF, 1) is a peptidyl nucleoside antibiotic produced by Streptomyces lavendulae. Studies were conducted to address the formation and timing of incorporation of the arginine-derived base streptolidine (4) during the biosynthesis of 1. [guanidino-(13)C]Streptolidine (10) was prepared by modification of an established method and used in whole-cell incorporation experiments. Analysis of the purified STF by (13)C NMR revealed a 1.9% enrichment of the guanidino carbon, confirming 4 as an advanced precursor to 1 and supporting proposals that 1 is assembled via a convergent biosynthetic pathway. To identify advanced intermediates in the conversion of L-arginine to 4, (2S,3R)-[guanidino-(13)C]capreomycidine (32) was prepared from oxazolidine aldehyde (18) via 1,1-dimethylethyl (4R,1'S)-4-(1',3'-diaminopropyl)-2,2-dimethyl-3-oxazolidinecarboxylate (30). Treatment of 30 with Br(13)CN yielded the corresponding diprotected amino alcohol, which was readily converted to 32. The STF isolated from whole-cell incorporation experiments with 32 showed no significant (13)C enrichment at the guanidino carbon. These results suggest that 32 may be an enzyme-bound intermediate, unable to enter the cell, or is not a precursor to STF.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jackson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gould
authors.forename: T Mark
authors.initials: TM
authors.lastname: Zabriskie
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis* / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002250:Carbon Radioisotopes; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D013309:Streptothricins / Q000096:biosynthesis* / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D006146:Guanidines; C463580:capreomycidine; C463579:guanidino-capreomycidine; C003349:streptolidine; C009156:streptothricin F; D013309:Streptothricins; D001120:Arginine