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 P-methoxyacrylate moiety.