Blasticidin S


Blasticidin S is an antibiotic that is produced by Streptomyces griseochromogenes. In biological research, specifically genetic engineering, it is used to select transformed cells which have been engineered to carry a resistance gene for blasticidin. In short, DNA of interest is fused to DNA encoding a resistance gene, and then is transformed into cells. After allowing time for recovery and for cells to begin transcribing and translating their new DNA, blasticidin is added. Now only the cells that have the new DNA can grow.

History

In the 1950s, a drug screening program was designed in Japan to discover a new antibiotic that prevents Blast Disease by the fungus Magnaporthe grisea.

Resistance genes

Three resistance genes have been cloned:
bsr and BSD are the most commonly used resistance genes. The proteins produced from these genes enable the cells carrying them to produce proteins in the presence of blasticidin.

Mechanism of action

Blasticidin prevents the growth of both eukaryotic and prokaryotic cells. It works by inhibiting termination step of translation and peptide bond formation by the ribosome. This means that cells can no longer produce new proteins through translation of mRNA. It is competitive with puromycin suggesting a highly similar binding site.

Biosynthesis

Cosmid cloning experiments from the Blasticidin S producer Streptomyces griseochromogenes, followed by evaluation of the putative biosynthetic gene cluster via heterologous reconstitution of Blasticidin S production in Streptomyces lividans, indicated that a 20 Kbp gene cluster with 19 genes, plus possibly a peptidase outside the gene cluster that acts on the final leucylblasticidin
S intermediate, was sufficient for reconstitution of Blasticidin S biosynthesis.