Onnamide A on:
[Wikipedia]
[Google]
[Amazon]
Onnamide A is a bioactive natural product found in ''Theonella swinhoei'', a species of marine sponge whose genus is well known for yielding a diverse set of biologically active natural products, including the swinholides and polytheonamides. It bears structural similarities to the pederins, a family of compounds known to inhibit protein synthesis in eukaryotic cells. Onnamide A and its analogues have attracted academic interest due to their cytotoxicity and potential for combating the growth and proliferation of cancer cells.
Genomic studies suggest strong homology with ''Ped'' genes, which encode the production of pederins, structurally similar compounds synthesized by bacterial endosymbionts of '' Paederus'' beetles. This suggests that onnamide A is actually the product of bacterial endosymbionts of the marine sponges from which the compound was first isolated. Thus, the biosynthetic pathway of onnamide A is envisioned to undertake analogous steps as those that lead to pederin, utilizing a prokaryotic PKS-NRPS system.
History
Onnamide A was first isolated in 1988 from ''Theonella spp.,'' a genus of marine sponges residing off the coast of Okinawa,Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
, as part of a bioassay aimed at discovering novel marine natural products possessing antiviral activity. Eight analogues possessing similar structure, as well as cytotoxicity were reported in 1992.
Structure
Onnamide A is a complex biomolecule with a 39 unique carbon atoms and 11 degrees of unsaturation. Its core contains three rings, two of which comprise a dimeric lactone structure. It contains a long side chain that has a three conjugated ''trans-'' olefins that connects to an amide bond, terminating in anarginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
residue. The stereochemical assignments of onnamide A have been extensively characterized by experimental and advanced NMR studies.
Biosynthesis
Genomic studies suggest strong homology with ''Ped'' genes, which encode the production of pederins, structurally similar compounds synthesized by bacterial endosymbionts of '' Paederus'' beetles. This suggests that onnamide A is actually the product of bacterial endosymbionts of the marine sponges from which the compound was first isolated. Thus, the biosynthetic pathway of onnamide A is envisioned to undertake analogous steps as those that lead to pederin, utilizing a prokaryotic PKS-NRPS system.
Cytotoxicity
Onnamide A inhibits protein synthesis in cell lines, leading to induction of stress-activated protein kinases apoptosis in the affected cell. Its derivatives have been found to be highly toxic towards leukemic cells of theP388 The NCI-60 cancer cell line panel is a group of 60 human cancer cell lines used by the National Cancer Institute (NCI) for the screening of compounds to detect potential anticancer activity.
Purpose
The screening procedure is called the NCI- ...
cell line.{{cite journal , author1=Shigeki Matsunaga , author2=Nobuhiro Fusetani , author3=Youichi Nakao , title=Eight New Cytotoxic Metabolites Closely Related to Onnamide A from Two Marine Sponges of the Genus Theonella , journal=Tetrahedron , volume=48 , issue=39 , pages=8369–8376 , year=1992 , doi=10.1016/S0040-4020(01)86585-6
See also
PederinReferences