Production of 8-Demethylgeldanamycin and 4,5-Epoxy-8-demethylgeldanamycin from a Recombinant Strain of Streptomyces hygroscopicus

Autor: Buchanan, G. O., Regentin, R., Piagentini, M., Rascher, A., McDaniel, R., Galazzo, J. L., Licari, P. J.
Zdroj: Journal of Natural Products; April 2005, Vol. 68 Issue: 4 p607-610, 4p
Abstrakt: Two new geldanamycin derivatives produced by genetic engineering of Streptomyces hygroscopicus strain K309-27-1 were isolated and characterized. Removal of the 8-methyl group of geldanamycin was achieved by replacing the AT4 domain of the polyketide synthase with a malonyl AT domain. The resulting strain produced 8-demethyl geldanamycin (2) and 4,5-epoxy-8-demethylgeldanamycin (3). The structures of both molecules were elucidated through interpretation of 1D and 2D NMR data as well as comparison with authentic geldanamycin derivatives. Compounds 2 and 3 displayed moderate cytotoxicity against the human breast cancer cell line SK-BR-3.
Databáze: Supplemental Index