Onnamide A
# Onnamide A

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.

## History

Onnamide A was first isolated in 1988 from Theonella spp., a genus of marine sponges residing off the coast of Okinawa, Japan, 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 an arginine 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 the P388 cell line.

