Pederin-type pathways of uncultivated bacterial symbionts: analysis of o-methyltransferases and generation of a biosynthetic hybrid.
The complex polyketide pederin is a potent antitumor agent isolated from Paederus spp. rove beetles. We have previously isolated a set of genes from a bacterial endosymbiont that are good candidates for pederin biosynthesis. To biochemically study this pathway, we expressed three methyltransferases from the putative pederin pathway and used the partially unmethylated analogue mycalamide A from the marine sponge Mycale hentscheli as test substrate. Analysis by high-resolution MS/MS and NMR revealed that PedO regiospecifically methylates the marine compound to generate the nonnatural hybrid compound 18-O-methylmycalamide A with increased cytotoxicity. To our knowledge, this is the first biochemical evidence that invertebrates can obtain defensive complex polyketides from bacterial symbionts.
Zimmermann
Katrin
K
Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
Engeser
Marianne
M
Blunt
John W
JW
Munro
Murray H G
MH
Piel
Jörn
J
D000818:Animals; D007941:Leukemia P388 / Q000188:drug therapy; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry / Q000378:metabolism; D011549:Pseudomonas / Q000235:genetics / Q000378:metabolism*; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013559:Symbiosis; D053719:Tandem Mass Spectrometry
D011714:Pyrans; C059646:mycalamide A; C100127:pederin; D008780:Methyltransferases