Paenimacrolidin, a novel macrolide antibiotic from Paenibacillus sp. F6‐B70 active against methicillin‐resistant Staphylococcus aureus

Summary Paenibacillus sp. F6‐B70 was selected from several dozens of isolates with activity against methicillin‐resistant Staphylococcus aureus using a 16S rDNA‐based screening method. F6‐B70 contained polyketide synthase (PKS) and non‐ribosomal peptide synthetase (NRPS) clusters in its genome revealed by PCR amplification of conserved adenylation and ketosynthase (KS) domains. Phylogenetic data suggested that the strain hosts trans ‐AT PKSs and their product may be a branched molecule. An antibiotic was subsequently isolated from the methanol extract of F6‐B70 cells. The molecular formula of the antibiotic was deduced to be C 33 H 50 NaO 6 ([M + Na] + , m/z 565.3505) by analysis of electrospray ionization mass spectral data. Elucidation of the structure by nuclear magnetic resonance and infrared spectroscopy revealed that the active compound, paenimacrolidin (PAM), was a novel 22‐membered macrolide with side‐chains. The new antibiotic, mainly as a bacteriostatic agent, inhibits a couple of multidrug‐resistant Staphylococcus sp. strains. The antibiotic capacity of PAM was compromised by its instability, which can be overcome significantly with addition of an anti‐oxidant. To our knowledge, this is the first report of the isolation of an active macrolide from paenibacilli, which may be a promising source of novel antibiotics.