[Disorazoles, potent cytotoxic compounds that disrupt microtubule formation]
>>Gene. 2005 Aug 2; [Epub ahead of print]
The biosynthetic genes for disorazoles, potent cytotoxic compounds that disrupt microtubule formation.
Carvalho R, Reid R, Viswanathan N, Gramajo H, Julien B.
Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, CA 94545, United States.
Disorazoles are polyketides produced by the myxobacterium Sorangium cellulosum So ce12. Their mode of action is to inhibit tubulin polymerization and destabilize microtubules. Using transposon mutagenesis, two mutant strains were identified that produced no disorazoles. Sequencing the DNA flanking the insertions revealed a polyketide synthase gene cluster that would encode three polypeptides, DszA, DszB, and DszC, with DszC containing both nonribosomal peptide synthetase and polyketide synthase modules. The disorazole polyketide synthase modules lack an acyltransferase domain. Instead, a separate gene, dszD, encodes an AT protein, thus revealing that the disorazole gene cluster falls into the trans-AT Type I family of PKS enzymes.<<
Obviously very early. Only three other citations -- starting in 2001 -- for disorazole. No idea how important this is.
Cheers, Tuck |
