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Self-Resistance During Muraymycin Biosynthesis: A Complementary Nucleotidyltransferase And Phosphotransferase With Identical Modification Sites And Distinct Temporal Order, Zheng Cui, Xia-Chang Wang, Xiaodong Liu, Anke Lemke, Stefan Koppermann, Christian Ducho, Jürgen Rohr, Jon S. Thorson, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Muraymycins are antibacterial natural products from Streptomyces spp. that inhibit translocase I (MraY), which is involved in cell wall biosynthesis. Structurally, muraymycins consist of a 5′-C-glycyluridine (GlyU) appended to a 5″-amino-5″-deoxyribose (ADR), forming a disaccharide core that is found in several peptidyl nucleoside inhibitors of MraY. For muraymycins, the GlyU-ADR disaccharide is further modified with an aminopropyl-linked peptide to generate the simplest structures, annotated as the muraymycin D series. Two enzymes encoded in the muraymycin biosynthetic gene cluster, Mur29 and Mur28, were functionally assigned in vitro as a Mg·ATP-dependent nucleotidyltransferase and a Mg·ATP-dependent phosphotransferase, respectively, both modifying the …