Planta Med 2014; 80 - PC36
DOI: 10.1055/s-0034-1382418

A new macrocyclic polyene antibiotic from Bacillus sp. AP183

R Ranga Rao 1, MR Jacob 1, X Chen 1, M Wang 1, S Nasrin 3, MR Liles 3, DA Mead 4, AK Agarwal 1, 2, IA Khan 1, 2, AM Clark 1, 2, XC Li 1, 2
  • 1National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences
  • 2Department of Biomolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA
  • 3Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA
  • 4Lucigen Corporation, Middleton, WI, USA

In our search for new antibiotics from soil microbes, Bacillus strain AP183 was shown to produce potent antibacterial activity against methicillin-resistant Staphylococcus aureus. This activity was not likely due to surfactins, iturins, and fengycins that are commonly present in Bacillus spp. as these antibiotic compounds generally exhibit weak or moderate antibacterial activities. Thus, bioassay-guided isolation from an organic extract (IC50 of < 20 µg/mL) of a 30-liter culture supernatant of this strain was conducted, leading to the discovery of a new macrocyclic polyene antibiotic (1) as a minor compound in 3.58 × 10-6 % of the crude extracts. Its structure was assigned by 1D and 2D NMR spectroscopic data as an unusual macrodiolide composed of dimeric 4-hydroxy-2-methoxy-6-alkenyl-benzoic acid lactones with conjugated pentaene-hexahydroxy polyketide chains. Compound 1 showed potent antibacterial activities against both drug sensitive and resistant S. aureus and Enterococcus faecalis with MICs ranging from 0.6 to1.2µg/mL. In vitro cytotoxicity assessment indicated that compound 1 was active against the mammalian Vero cell line with an IC50 of 0.71µg/mL. These activity profiles are comparable to those of the structurally similar analog marinomycin A isolated from a marine Actinobacteria.