Figure 5

Metabolic pathway of vancomycin biosynthesis. Three steps are involved in the biosynthesis of vancomycin, and the related functional genes in and outside of the vcm cluster were mapped. I) The biosynthesis of its amino-acid precursors (right of the panel). Non-ribosomal peptide synthetase VcmD (AORI_1493) catalyzes free tyrosines to form tyrosyl-S-enzyme, which is hydroxylated by OxyD (AORI_1494) and then release as βHt by the action of Vhp (AORI_1492). Genes of pdh/hpgT/hmaS/hmO (AORI_1476, AORI_1491, AORI_1495-1496) are responsible for Hpg synthesis from prephenate, and dpgA/B/C/D (AORI_1502-AORI_1505) are responsible for Dpg synthesis using malonyl-CoA as the starting unit. II) The modified amino acids are assembled to form linear heptapeptide by NRPSs (VcmABC, AORI_1478-1480) with seven modules (M1-M7, upper left of the panel). A, adenylation domain; C, condensation domain; E, epimerization domain; T, thiolation domain; TE, thioesterase domain. III) The post-modifications of the linear heptapeptide (down the left side of the panel) include cyclization (oxyA/B/C, AORI_1482-AORI_1484), halogenation (vhal, AORI_1485), methylation (vmt, AORI_1490), and glycosylation (gtfDE, AORI_1486-AORI_1487). Finally, vancomycin is generated.