TDP-mycaminose biosynthetic pathway revised and conversion of desosamine pathway to mycaminose pathway with one gene.
Analysis of the tylosin gene cluster in Streptomyces fradiae uncovered an ORF, tyl1a, homologous to a hexose 3,4-isomerase found in Aneurinibacillus thermoaerophilus. Inclusion of the tyl1a gene along with other mycaminose biosynthetic genes (tylB, tylM1, tylM2, tylM3) identified in previous studies in an in vivo expression system successfully reconstituted the mycaminose pathway. Expression of tyl1a alone in the S venezuelae KdesI mutant converted a desosamine pathway to a mycaminose pathway. These results strongly support the role of Tyl1a as a TDP-4-keto-6-deoxy-d-glucose 3,4-isomerase.
Melançon
Charles E
CE
Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
Yu
Wei-luen
WL
Liu
Hung-wen
HW
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D005798:Genes, Bacterial; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008956:Models, Chemical; D005810:Multigene Family; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D009702:Nucleoside Diphosphate Sugars; C100183:thymidine diphosphate sugars; C013610:mycaminose; D005944:Glucosamine