Complete characterization of the seventeen step moenomycin biosynthetic pathway

摘要: The moenomycins are phosphoglycolipid antibiotics produced by Streptomyces ghanaensis and related organisms. phosphoglycolipids the only known active site inhibitors of peptidoglycan glycosyltransferases, an important family enzymes involved in biosynthesis bacterial cell wall. Although these natural products have exceptionally potent antibiotic activity, pharmacokinetic limitations precluded their clinical use. We previously identified moenomycin biosynthetic gene cluster order to facilitate approaches new derivatives. Here, we report a comprehensive set genetic enzymatic experiments that establish functions for 17 genes synthesis variants. These studies reveal assembly full molecular scaffold define subset seven bioactive analogues. This work will enable both vitro fermentation-based reconstitution scaffolds so chemoenzymatic novel analogues can be explored.