Lactacystin is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

naturally synthesized by

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

of the

genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

'' first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. (1991). Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al. ''J. Antibiot.'' 44(1):113-6. The target of lactacystin was subsequently found to be the

proteasome Proteasomes are essential protein complexes responsible for the degradation of proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are found inside all e ...

on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995. The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. Lactacystin was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. The transformation product of lactacystin clasto-lactacystin β-lactone (also known as omuralide) covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery that helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal

threonine protease Threonine proteases are a family of proteolytic enzymes harbouring a threonine (Thr) residue within the active site. The prototype members of this class of enzymes are the catalytic subunits of the proteasome, however, the acyltransferases conve ...

. The molecule is commonly used in

biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...

and

cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...

laboratories as a selective inhibitor of the

. The first

total synthesis Total synthesis, a specialized area within organic chemistry, focuses on constructing complex organic compounds, especially those found in nature, using laboratory methods. It often involves synthesizing natural products from basic, commercially ...

of lactacystin was developed in 1992 by Corey and Reichard,''"Total Synthesis of Lactacystin"'' Corey, E. J.; Reichard, G. A. '' J. Am. Chem. Soc.'' 1992, ''114'', 10677. and a number of other syntheses of this molecule have also been published. There are more than 1,660 entries for lactacystin in

PubMed PubMed is an openly accessible, free database which includes primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institute ...

as of January 2019.

References

{{Reflist Acetamides Pyrrolidones Secondary alcohols Total synthesis Lactams

See also

References