Leptomycin
Encyclopedia
Leptomycin B is a secondary metabolite
produced by Streptomyces
spp.
Leptomycin B (LMB) was originally discovered as a potent anti-fungal antibiotic
. Leptomycin B was found to cause cell elongation of the fission yeast Schizosaccharomyces pombe
. Since then this elongation effect has been used for the bioassay
of leptomycin. However, recent data (2003) shows that Leptomycin causes G1 cell cycle arrest in mammalian cells and is a potent anti-tumor agent against murine experimental tumors.
Leptomycin B has been shown to be a potent and specific nuclear export inhibitor in human and the fission yeast Schizosaccharomyces pombe
. Leptomycin B alkylates and inhibits CRM1 (chromosomal region maintenance)/exportin 1 , a protein required for nuclear export of proteins containing a nuclear export sequence (NES), by glycosylating a cysteine
residue (cysteine 529 in S. pombe). In addition to antifungal and antibacterial activities, Leptomycin B blocks the cell cycle and is a potent anti-tumor agent. At low nM concentrations, Leptomycin B blocks the nuclear export of many proteins including HIV-1 Rev, MAPK/ERK, and NF-κB/IκB, and it inhibits the inactivation of p53
. Leptomycin B also inhibits the export and translation of many RNA
s, including COX-2 and c-Fos
mRNAs, by inhibiting export of ribonucleoprotein
s.
Leptomycin A (LPA) was discovered together with LMB. LMB is twice as potent as LPA.
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Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
produced by Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
spp.
Leptomycin B (LMB) was originally discovered as a potent anti-fungal 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...
. Leptomycin B was found to cause cell elongation of the fission yeast Schizosaccharomyces pombe
Schizosaccharomyces pombe
Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast. It is used as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length...
. Since then this elongation effect has been used for the bioassay
Bioassay
Bioassay , or biological standardization is a type of scientific experiment. Bioassays are typically conducted to measure the effects of a substance on a living organism and are essential in the development of new drugs and in monitoring environmental pollutants...
of leptomycin. However, recent data (2003) shows that Leptomycin causes G1 cell cycle arrest in mammalian cells and is a potent anti-tumor agent against murine experimental tumors.
Leptomycin B has been shown to be a potent and specific nuclear export inhibitor in human and the fission yeast Schizosaccharomyces pombe
Schizosaccharomyces pombe
Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast. It is used as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length...
. Leptomycin B alkylates and inhibits CRM1 (chromosomal region maintenance)/exportin 1 , a protein required for nuclear export of proteins containing a nuclear export sequence (NES), by glycosylating a cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residue (cysteine 529 in S. pombe). In addition to antifungal and antibacterial activities, Leptomycin B blocks the cell cycle and is a potent anti-tumor agent. At low nM concentrations, Leptomycin B blocks the nuclear export of many proteins including HIV-1 Rev, MAPK/ERK, and NF-κB/IκB, and it inhibits the inactivation of p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
. Leptomycin B also inhibits the export and translation of many RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
s, including COX-2 and c-Fos
C-Fos
In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...
mRNAs, by inhibiting export of ribonucleoprotein
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
s.
Leptomycin A (LPA) was discovered together with LMB. LMB is twice as potent as LPA.
External links
Original data copied with permission from Leptomycin B manufacturer product page (FermentekFermentek
Fermentek Ltd. is a biotechnological company, located in Atarot industrial zone, Jerusalem, Israel, specializing in the research, development and manufacture of biologically active, natural products isolated from microorganisms as well as from other natural sources such as plants and algae.The main...
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