Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli.
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.
Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, P.O. Box 15115, 66041 Saarbrücken, Germany.
Xiaoying
X
Bian
Alberto
A
Plaza
Youming
Y
Zhang
Rolf
R
Müller
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D055088:Early Detection of Cancer; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification*; D020637:Photorhabdus / Q000737:chemistry*
D000970:Antineoplastic Agents; D001688:Biological Products; D009842:Oligopeptides; C577387:luminmycin A; C577388:luminmycin B; C577389:luminmycin C