title: Production of cytotoxic glidobactins/luminmycins by Photorhabdus asymbiotica in liquid media and live crickets.
abstract: Photorhabdus asymbiotica engages in a two-part life cycle that requires adaptation to both symbiotic and pathogenic phases. The genome of P. asymbiotica contains several gene clusters, which are predicted to be involved in the biosynthesis of unique secondary metabolites that are hypothesized to enhance the bacterium's pathogenic capabilities. However, recent reports on Photorhabdus secondary metabolite production have indicated that many of its genes are silent under laboratory culture conditions. Using a circumscribed panel of media and alternative fermentation conditions, we have successfully achieved the production of a series of new and known glidobactin/luminmycin derivatives from P. asymbiotica including glidobactin A (1), luminmycin A (2), and luminmycin D (3). These compounds were also obtained upon infection of live crickets with the bacterium. Luminmycin D showed cytotoxicity against human pancreatic cells (IC50 of 0.11 μM), as well as proteasome inhibition (IC50 of 0.38 μM).
authors.affiliation: Natural Products Discovery Group, Institute for Natural Products Applications and Research Technologies, Stephenson Life Sciences Research Center, 101 Stephenson Parkway, University of Oklahoma , Norman, Oklahoma 73019-5251, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Theodore
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: King
authors.forename: Jianlan
authors.initials: J
authors.lastname: You
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D000818:Animals; D004354:Drug Screening Assays, Antitumor; D006135:Gryllidae / Q000382:microbiology*; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification; D020637:Photorhabdus / Q000737:chemistry* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; C577387:luminmycin A; C057878:glidobactin A; D046988:Proteasome Endopeptidase Complex