Miuraenamides: antimicrobial cyclic depsipeptides isolated from a rare and slightly halophilic myxobacterium.

Marine myxobacteria are rare culture-resistant microorganisms, several strains of which have been identified by research groups in Asia. Paraliomyxa miuraensis, a slightly halophilic myxobacterium discovered in Japan, produces the cyclic hybrid polyketide-peptide antibiotics known as miuraenamides A and B, whose taxonomical and biological characteristics have been reported previously. Herein, we describe the chemical characterization of these two miuraenamides and introduce four new members of the miuraenamide family. We carried out the complete structural analysis of miuraenamides A and B on the basis of NMR spectroscopic analysis and elucidated the absolute configuration of miuraenamide A by chemical derivatization and subsequent use of the modified Mosher method or the Marfey method. Miuraenamides C-F were isolated from the same strain of the bacterium as miuraenamides A and B. The structure-antimicrobial-activity relationships of the six natural metabolites and four chemically derived compounds demonstrated the importance of both the macrocyclic structure and the beta-methoxyacrylate moiety.

Miuraenamides A and B, novel antimicrobial cyclic depsipeptides from a new slightly halophilic myxobacterium: taxonomy, production, and biological properties.

A slightly halophilic myxobacterial strain, SMH-27-4, was isolated from nearshore soil and shown to belong to a new myxobacterium genus based on phylogenetic analysis. This slowly-growing myxobacterium produced the novel antibiotic depsipeptides miuraenamides A and B. Their physico-chemical properties and molecular formulas, C34H42N3O7Br and C34H42N3O7I, were determined. Miuraenamides A exhibited potent and selective inhibition against a phytopathogenic microorganism, Phytophthora sp., and moderate inhibition against some fungi and yeasts, but was ineffective against bacteria. Both of the metabolites inhibited NADH oxidase at IC50 values of 50 microM, suggesting, like beta-methoxyacrylate-type antibiotics, the electron transfer system of the mitochondrial respiratory chain as the cellular target.