Elucidation of a carboxylate O-methyltransferase NcmP in nocamycin biosynthetic pathway

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4431-4435. doi: 10.1016/j.bmcl.2017.08.010. Epub 2017 Aug 7.


Nocamycins belong to the tetramic acid family natural products and show potent antimicrobial activity. Recently, the biosynthetic gene cluster of nocamycin was identified from the rare actinomycete Saccharothrix syringae and an S-adenosylmethionine (SAM) dependent methyltransferase gene NcmP was found to be located within the gene cluster. In this report, the methyltransferase gene NcmP was disrupted and a new nocamycin intermediate nocamycin E was isolated from the mutant strain. Meanwhile, NcmP was heterologously expressed in Escherichia coli BL21 (DE3) and biochemically characterized as a carboxylate O-methyltransferase in nocamycin biosynthetic pathway. Compared to nocamycin I, nocamycin E showed inferior antibacterial activity, indicating the methyl group is essential to antibacterial activity.

Keywords: Antibacterial activity; Enzyme reaction; Methyltransferase; Nocamycins; Post-tailoring modification.

MeSH terms

  • Actinomycetales / genetics
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Bacillus / drug effects
  • Dose-Response Relationship, Drug
  • Enterococcus faecalis / drug effects
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Microbial Sensitivity Tests
  • Micrococcus luteus / drug effects
  • Molecular Structure
  • Organic Chemicals / chemistry
  • Organic Chemicals / metabolism*
  • Organic Chemicals / pharmacology
  • Polyketides
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Organic Chemicals
  • Polyketides
  • nocamycin
  • Methyltransferases