Macrolactams are made by feeding aromatic amino acids as replacement starter units to a mutant strain of the geldanamycin-producing microorganism
Streptomyces hygroscopicus
var.
geldanus
NRRL 3602, wherein the gene cluster encoding enzymes for the biosynthesis of the natural starter unit 3-amino-5-hydroxybenzoic acid has been deleted.
Potent Non-Benzoquinone Ansamycin Heat Shock Protein 90 Inhibitors from Genetic Engineering of <i>Streptomyces hygroscopicus</i>
作者:Hugo G. Menzella、Thomas-Toan Tran、John R. Carney、Janice Lau-Wee、Jorge Galazzo、Christopher D. Reeves、Christopher Carreras、Sophie Mukadam、Sara Eng、Ziyang Zhong、Pieter B. M. W. M. Timmermans、Sumati Murli、Gary W. Ashley
DOI:10.1021/jm900012a
日期:2009.3.26
Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy. We describe the preparation of potent non-benzoquinone ansamycins. One of these analogues, generated by feeding 3-amino-5-chlorobenzoic acid to a genetically engineered strain of Streptomyces hygroscopicus, shows high accumulation and long residence time in tumor tissue, is well-tolerated upon intravenous dosing, and is highly efficacious in the COLO205 mouse tumor xenograft model.