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

Microb Biotechnol. 2011 Jul;4(4):491-502. doi: 10.1111/j.1751-7915.2010.00201.x. Epub 2010 Aug 19.

Abstract

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.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Cluster Analysis
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Macrolides / chemistry
  • Macrolides / isolation & purification*
  • Macrolides / metabolism
  • Macrolides / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Metabolic Networks and Pathways / genetics
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Molecular Sequence Data
  • Molecular Structure
  • Multigene Family
  • Paenibacillus / classification
  • Paenibacillus / isolation & purification*
  • Paenibacillus / metabolism*
  • Phylogeny
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, DNA
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • DNA, Ribosomal
  • Macrolides
  • RNA, Ribosomal, 16S

Associated data

  • GENBANK/GQ240305
  • GENBANK/GQ262803
  • GENBANK/GQ262804
  • GENBANK/GQ262805
  • GENBANK/GQ262806
  • GENBANK/GQ262807
  • GENBANK/GQ262808
  • GENBANK/GQ262809
  • GENBANK/GQ262810
  • GENBANK/GQ262811