Borissow Charles N, Graham Cathy L, Syvitski Ray T, Reid Taryn R, Blay Jonathan, Jakeman David L
College of Pharmacy, Burbidge Building, Dalhousie University, 5968 College Street, Halifax, Nova Scotia, B3H 3J5, Canada.
Chembiochem. 2007 Jul 9;8(10):1198-203. doi: 10.1002/cbic.200700204.
The jadomycins are a series of natural products produced by Streptomyces venzuelae ISP5230 in response to ethanol shock. A unique structural feature of these angucyclines is the oxazolone ring, the formation of which is catalyzed by condensation of a biosynthetic aldehyde intermediate and an amino acid. The feeding of enantiomeric forms of alpha-amino acids indicates that the amino acid is incorporated by S. venezuelae ISP5230 without isomerization at the alpha-carbon. The characterization of the first two six-membered E-ring-containing jadomycins is reported. These precursor-directed biosynthesis studies indicate flexibility in the acceptor substrate specificity of the glycosyltransferase, JadS. Analysis of cytotoxicity data against two human breast cancer cell lines indicates that the nature of the substitution at the alpha-carbon, rather than the stereochemistry, influences biological activity.
柔红霉素是委内瑞拉链霉菌ISP5230在乙醇冲击下产生的一系列天然产物。这些安古霉素类化合物的一个独特结构特征是恶唑酮环，其形成是由生物合成醛中间体与氨基酸缩合催化的。对映体形式的α-氨基酸的饲喂表明，该氨基酸被委内瑞拉链霉菌ISP5230掺入，且在α-碳处没有异构化。报道了前两种含六元E环的柔红霉素的表征。这些前体导向的生物合成研究表明糖基转移酶JadS的受体底物特异性具有灵活性。对两种人乳腺癌细胞系的细胞毒性数据分析表明，α-碳处取代的性质而非立体化学影响生物活性。
