Disease relevance of Pederin

• However, we have recently identified an uncultured Pseudomonas sp. symbiont as the most likely producer of the defensive antitumor polyketide pederin in Paederus fuscipes beetles by cloning the putative biosynthesis genes [1].
• On the basis of preliminary results described herein, we speculate that, despite their structural resemblance, psymberin and pederin/mycalamide induce toxicity through different mechanisms [2].
• Short-term exposure of squamous carcinoma cells to 18-O-methyl mycalamide B or pederin caused an irreversible inhibition of cellular proliferation and induced cellular necrosis [3].
• Crushing PF on the skin causes acute dermatitis within 24 hours, corresponding in shape and dimensions to the area affected by the substance released (pederin) [4].
• The presence of some acantholytic foci, relatively far from the foci of clinically involved skin, in four of the cases considered suggests a possible role of pederin in inducing acantholysis indirectly [4].

High impact information on Pederin

• The ped cluster, which is present only in beetle specimens with high pederin content, is located on a 54-kb region bordered by transposase pseudogenes and encodes a mixed modular polyketide synthase/nonribosomal peptide synthetase [5].
• Evidence for a symbiosis island involved in horizontal acquisition of pederin biosynthetic capabilities by the bacterial symbiont of Paederus fuscipes beetles [6].
• We have sequenced an extended region of the symbiont genome to gain further insight into the biology of this as-yet-unculturable bacterium and the evolution of pederin symbiosis [6].
• However, a recent analysis of the putative pederin biosynthesis (ped) gene cluster strongly suggests that pederin is produced by bacterial symbionts [6].
• It contains at least three novel catalytic domains that are predicted to be involved in pederin chain initiation and the formation of an unusual exomethylene bond [7].

Chemical compound and disease context of Pederin

• Evaluation of antiproliferative activity reveals that the dihydroisocoumarin fragment is important for psymberin toxicity and the cyclic pederate fragment is important for pederin/mycalamide toxicity [2].

Biological context of Pederin

• Interestingly, competition studies demonstrated that 13-deoxytedanolide shared the binding site on the 60S large subunit with pederin and its marine-derived analogues [8].

Anatomical context of Pederin

• The activities of 18-O-methyl mycalamide B and pederin were virtually indistinguishable when evaluated in DNA or protein synthesis assays, and in cytotoxicity assays using human carcinoma cell lines (IC50s 0.2-0.6 nM) [3].
• Biosynthesis of the structurally complex hemolymph toxin pederin is an eminent character of Paederus females [9].

References