Structural diversity, bioactivity, and biosynthesis of phosphoglycolipid family antibiotics: Recent advances

Mechanistic Insights into the Activities of Major Families of Enzymes in Bacterial Peptidoglycan Assembly and Breakdown

“…Moenomycin, which is a natural product phosphoglycolipid, represents the only known class of PGT (i. e., aPBPs and MGTs) inhibitors with excellent in vitro activities. [55] Moenomycin A (MoeA) is the founding member of the family. It contains a 3phosphoglyceric acid (3-PG) core, with an isoprenoid chain attached to the C2-OH of 3-PG and a complex pentasaccharide unit at the phosphate group of 3-PG.…”

“…It contains a 3phosphoglyceric acid (3-PG) core, with an isoprenoid chain attached to the C2-OH of 3-PG and a complex pentasaccharide unit at the phosphate group of 3-PG. [55] The structural resemblance of MoeA with the growing peptidoglycan strand substrate (Lipid IV) has led to the proposal that MoeA is an active site inhibitor. Correspondingly, several crystal and CryoEM structures of MoeA-bound PGTs (i. e., aPBPs and MGTs) revealed that MoeA resides in the glycosyl donor site and its carbohydrate and 3-PG moieties are extensively hydrogen bonded to a number of residues in the active site, locking the PGT into an inactive conformation.…”

“…On the other hand, the presence of the lipid tail and hence the lipophilic nature of MoeA renders it undesirable pharmacokinetic properties for clinical applications. [55] Thus, many efforts have been devoted to the discovery of alternative scaffolds for PGT inhibitors. [61,62] For instance, based on the minimal pharmacophore of MoeA, Gampe et al developed a fluorescent probe using a truncated MoeA analogue for high-throughput screening of potential PGT inhibitors.…”

“…Moenomycin, which is a natural product phosphoglycolipid, represents the only known class of PGT (i. e., aPBPs and MGTs) inhibitors with excellent in vitro activities [55] . Moenomycin A (MoeA) is the founding member of the family.…”

“…Moenomycin A (MoeA) is the founding member of the family. It contains a 3‐phosphoglyceric acid (3‐PG) core, with an isoprenoid chain attached to the C2‐OH of 3‐PG and a complex pentasaccharide unit at the phosphate group of 3‐PG [55] . The structural resemblance of MoeA with the growing peptidoglycan strand substrate (Lipid IV) has led to the proposal that MoeA is an active site inhibitor.…”