Polyether biosynthesis. 2. Origin of the oxygen atoms of monensin A

Identification of a Gene Cluster of Polyether Antibiotic Lasalocid fromStreptomyces lasaliensis

“…9) In biosynthetic studies on another important polyether ionophore, monensin, this insightful hypothesis was supported by extensive incorporation experiments with [1-13 C,1-18 O]-short chain fatty acids and 18 O 2 , indicating that the terminal three oxygen atoms were derived from corresponding epoxidation of the triene precursor as shown in Scheme 1B. 10) These data led to the Cane-Celmer-Westley unified hypothesis of ionophore polyether biosynthesis in actinomycetes. 1) After this proposal, several groups attempted to incorporate advanced polyene intermediates.…”

Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization

“…Experiments using carbon‐14‐labelled precursors have shown that monensin A is synthesized from five acetate, one butyrate and seven propionate units (Day et al ., 1973). Similarly, experiments using precursors doubly‐labelled with carbon‐13 and oxygen‐18 have shown that oxygens (O)1, (O)3, (O)4, (O)5, (O)6 and (O)10 of monensin arise from the carboxylate oxygens of either propionate or acetate, while growth in the presence of oxygen‐18 gas demonstrated that the three remaining ether oxygens (O)7, (O)8 and (O)9 are derived from molecular oxygen (Cane et al ., 1981; Cane et al ., 1982; Ajaz and Robinson, 1983).…”

Nature as organic chemist

“…44 Turning to polyether antibiotics, we also established the derivation of all the oxygens in monensin (15) and the closely related lenoremycin from acetate, propionate or molecular oxygen (Figure 9). 45,46 On the basis of these latter discoveries, we extended an original suggestion of Dr John Westley of Hoffman-La Roche for the biosynthesis of lasalocids and proposed a general stereochemical model of polyether biosynthesis, involving the nucleophilic cascade cyclization of polyepoxide intermediates derived from an initially formed all-E-unsaturated polyketide ( Figure 9). 47 In recent years, this biosynthetic hypothesis has been strongly validated by an array of independent molecular genetic, biochemical, and structural biological studies by Prof Peter Leadlay 48,49 at the University of Cambridge and Prof Hideaki Oikawa 50,51 at the University of Hokkaido.…”