Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli

J Nat Prod. 2012 Sep 28;75(9):1652-5. doi: 10.1021/np300444e. Epub 2012 Aug 21.

Abstract

The 18 kb "silent" luminmycin biosynthetic pathway from Photorhabdus luminescens was cloned into a vector by using the newly established linear-linear homologous recombination and successfully expressed in Escherichia coli. Luminmycins A-C (1-3) were isolated from the heterologous host, and their structures were elucidated using 2D NMR spectroscopy and HRESIMS. Luminmycin A is a deoxy derivative of the previously reported glidobactin A, while luminmycins B and C most likely represent its acyclic biosynthetic intermediates. Compound 1 showed cytotoxicity against the human colon carcinoma HCT-116 cell line with an IC(50) value of 91.8 nM, while acyclic 2 was inactive at concentrations as high as 100 μg/mL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology
  • Early Detection of Cancer
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • HCT116 Cells
  • Humans
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligopeptides / chemistry
  • Oligopeptides / isolation & purification*
  • Photorhabdus / chemistry*

Substances

  • Antineoplastic Agents
  • Biological Products
  • Oligopeptides
  • luminmycin A
  • luminmycin B
  • luminmycin C