Anti-MRSA and anti-TB metabolites from marine-derived Verrucosispora sp. MS100047

Appl Microbiol Biotechnol. 2016 Sep;100(17):7437-47. doi: 10.1007/s00253-016-7406-y. Epub 2016 Mar 15.

Abstract

Microbes belonging to the genus Verrucosispora possess significant chemical diversity and biological properties. They have attracted the interests of many researchers and are becoming promising resources in the marine natural product research field. A bioassay-guided isolation from the crude extract of Verrucosispora sp. strain MS100047, isolated from sediments collected from the South China Sea, has led to the identification of a new salicylic derivative, glycerol 1-hydroxy-2,5-dimethyl benzoate (1), along with three known compounds, brevianamide F (2), abyssomicin B (3), and proximicin B (4). Compound 1 showed selective activity against methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) value of 12.5 μg/mL. Brevianamide F (2), which was isolated from actinomycete for the first time, showed a good anti-BCG activity with a MIC value of 12.5 μg/mL that has not been reported previously in literatures. Proximicin B (4) showed significant anti-MRSA (MIC = 3.125 μg/mL), anti-BCG (MIC = 6.25 μg/mL), and anti-tuberculosis (TB) (MIC = 25 μg/mL) activities. This is the first report on the anti-tubercular activities of proximicins. In addition, Verrucosispora sp. strain MS100047 was found to harbor 18 putative secondary metabolite gene clusters based on genomic sequence analysis. These include the biosynthetic loci encoding polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) consistent with abyssomicins and proximicins, respectively. The biosynthetic pathways of these isolated compounds have been proposed. These results indicate that MS100047 possesses a great potential as a source of active secondary metabolites.

Keywords: Anti-BCG; Anti-MRSA; Marine-derived Verrucosispora; Salicylic derivative.

MeSH terms

  • Antitubercular Agents / isolation & purification
  • Antitubercular Agents / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / isolation & purification
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Geologic Sediments / microbiology
  • Glycerides / isolation & purification
  • Glycerides / pharmacology*
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / pharmacology
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Micromonosporaceae / metabolism*
  • Mycobacterium bovis / drug effects*
  • Netropsin / analogs & derivatives
  • Netropsin / isolation & purification
  • Netropsin / pharmacology
  • Peptide Synthases / genetics*
  • Polyketide Synthases / genetics*
  • Salicylates / chemistry
  • Salicylates / isolation & purification
  • Salicylates / pharmacology*

Substances

  • Antitubercular Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Glycerides
  • Indole Alkaloids
  • Salicylates
  • brevianamide F
  • glycerol 1-hydroxy-2,5-dimethyl benzoate
  • proximicin B
  • Netropsin
  • Polyketide Synthases
  • Peptide Synthases
  • non-ribosomal peptide synthase