Identification of the Enzymes Mediating the Maturation of the Seryl-tRNA Synthetase Inhibitor SB-217452 during the Biosynthesis of Albomycins

Albomycin δ₂ is a sulfur-containing sideromycin natural product that shows potent antibacterial activity against clinically important pathogens. The l -serine-thioheptose dipeptide partial structure, known as SB-217452, has been found to be the active seryl-tRNA synthetase inhibitor component of albomycin δ₂. Herein, it is demonstrated that AbmF catalyzes condensation between the 6′-amino-4′-thionucleoside with the d -ribo configuration and seryl-adenylate supplied by the serine adenylation activity of AbmK. Formation of the dipeptide is followed by C3′-epimerization to produce SB-217452 with the d -xylo configuration, which is catalyzed by the radical S-adenosyl-l -methionine enzyme AbmJ. Gene deletion suggests that AbmC is involved in peptide assembly linking SB-217452 with the siderophore moiety. This study establishes how the albomycin biosynthetic machinery generates its antimicrobial component SB-217452.     

15‐Hydroperoxy‐PGE2: Intermediate in Mammalian and Algal Prostaglandin Biosynthesis

Arachidonic‐acid‐derived prostaglandins (PGs), specifically PGE₂, play a central role in inflammation and numerous immunological reactions. The enzymes of PGE₂ biosynthesis are important pharmacological targets for anti‐inflammatory drugs. Besides mammals, certain edible marine algae possess a comprehensive repertoire of bioactive arachidonic‐acid‐derived oxylipins including PGs that may account for food poisoning. Described here is the analysis of PGE₂ biosynthesis in the red macroalga Gracilaria vermiculophylla that led to the identification of 15‐hydroperoxy‐PGE₂, a novel precursor of PGE₂ and 15‐keto‐PGE₂. Interestingly, this novel precursor is also produced in human macrophages where it represents a key metabolite in an alternative biosynthetic PGE₂ pathway in addition to the well‐established arachidonic acid‐PGG₂‐PGH₂‐PGE₂ route. This alternative pathway of mammalian PGE₂ biosynthesis may open novel opportunities to intervene with inflammation‐related diseases.