Anisomycin, also known as flagecidin is an antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 produced by Streptomyces griseolus which inhibits protein synthesis

Translation (genetics)

In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

. Partial inhibition

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

 of DNA synthesis

DNA synthesis

DNA synthesis commonly refers to:*DNA replication - DNA biosynthesis *Polymerase chain reaction - enzymatic DNA synthesis *Oligonucleotide synthesis - chemical synthesis of nucleic acids...

 occurs at anisomycin concentration

Concentration

In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s that effect 95% inhibition of protein synthesis. Anisomycin can activate stress-activated protein kinases, MAP kinase and other signal transduction

Signal transduction

Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 pathways.

Anisomycin is inactive against bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

.

Pharmacology

Anisomycin interferes with protein and DNA synthesis by inhibiting peptidyl transferase

Peptidyl transferase

The Peptidyl transferase is an aminoacyltransferase as well as the primary enzymatic function of the ribosome, which forms peptide links between adjacent amino acids using tRNAs during the translation process of protein biosynthesis....

 or the 80S ribosome

Ribosome

A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 system.

Anisomycin is also mentioned as a potential psychiatric drug, as it may inhibit the consolidation of new context-specific long-term memories.".

Injection of anisomycin into the hippocampus

Hippocampus

The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

has been proposed for selective removal of memories.

Biosynthesis

Despite anisomycin's wide usage as a protein biosynthesis inhibitor, there have been few studies centered around the biosynthesis of anisomycin. One study by Butler in 1965 proposed possible precursors to this natural product. Fermentation of Streptomyces with labeled amino acids was followed by a degradation of the radioactive anisomycin and deacetylanisomycin products to determine the locations of the labeled carbons. Although its pyrrolidine-based structure suggests that it is derived from proline, the results from the experiments indicated that tyrosine, glycine, methionine, and acetate are the primary precursors for the biosynthesis of anisomycin. Tyrosine and, to a limited degree, phenylalanine, contribute to C-2 of the pyrrolidine ring. Methionine is likely responsible for the methylation of the hydroxyl group on the aromatic ring as S-adenosylmethionine (SAM). Glycine or acetate account for C-4 and C-5 on the pyrrolidine ring. It was noted that deacetylanisomycin was a prominent product in the first few days of fermentation, suggesting that acetylation of the C-3 hydroxyl group by acetyl Co-A is the final step in the biosynthesis of anisomycin. The source of the nitrogen within the ring and C-3 were undetermined. However, C-3 is not likely to be provided by the carboxylic acid group of tyrosine because tracking of radioactivity indicated that tyrosine undergoes decarboxylation during fermentation.

Other uses

Anisomycin is used as a component of Martin Lewis Agar, an in- vitro diagnostic product which is used extensively in the United States for the selective isolation of Neisseria gonorrhoeae and Neisseria meningitidis.

Using a novel high-throughput screening assay, Mawji et al. showed that anisomycin can sensitize metastatic epithelial cells to anoikis and reduce circulating tumor cell implantation in vivo. Anisomycin achieved this anti-metastatic activity in part by decreasing the abundance of the death receptor inhibiting protein FLIP. In related work, Mawji's team showed that FLIP levels are higher in metastatic cells than non-metastatic cells, and that reducing FLIP levels using RNAi (RNA Interference) or other small molecule inhibitors of FLIP can sensitize metastatic cells to anoikis. Given that FLIP is an inhibitor of anoikis, and that reducing FLIP can sensitize metastatic cells to anoikis, Mawji et al. hypothesize that FLIP reduction may be a viable therapeutic strategy against cancer metastasis.