Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen , Meston Walk, Aberdeen AB24 3UE, Scotland, UK.
J Nat Prod. 2011 Jun 24;74(6):1491-9. doi: 10.1021/np200320u. Epub 2011 May 9.
Streptomyces sp. strain C34, isolated from soil collected in the Chilean hyper-arid Atacama Desert, was cultured on different media, resulting in the isolation and identification of four new ansamycin-type polyketides. The organism was selected for chemical investigation on the basis of a genome-mining PCR-based experiment targeting the gene encoding rifamycin-specific 3-amino-5-hydroxybenzoic acid synthetase (AHBA). The isolated compounds were structurally characterized using NMR and MS techniques and named chaxamycins A-D (1-4). Compounds 1-4 were tested for their antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and for their ability to inhibit the intrinsic ATPase activity of the heat shock protein 90 (Hsp90). Chaxamycin D (4), which showed a selective antibacterial activity against S. aureus ATCC 25923, was tested further against a panel of MRSA clinical isolates. In a virtual screening experiment, chaxamycins A-D (1-4) have also been docked into the ATP-binding pocket in the N-terminal domain of the Hsp90, and the observed interactions are discussed.
从智利极端干旱的阿塔卡马沙漠采集的土壤中分离到的链霉菌 C34 菌株，在不同的培养基上进行培养，分离和鉴定了四种新的安莎霉素型聚酮化合物。该生物体是根据针对 Rifamycin 特异性 3-氨基-5-羟基苯甲酸合酶（AHBA）编码基因的基于基因组挖掘 PCR 的实验进行化学研究选择的。使用 NMR 和 MS 技术对分离得到的化合物进行结构表征，并将其命名为 chaxamycins A-D（1-4）。测试了化合物 1-4 对金黄色葡萄球菌 ATCC 25923 和大肠杆菌 ATCC 25922 的抗菌活性，以及它们抑制热休克蛋白 90（Hsp90）内在 ATP 酶活性的能力。对具有选择性抗金黄色葡萄球菌 ATCC 25923 活性的 chaxamycin D（4）进行了进一步测试，以检测其对一系列耐甲氧西林金黄色葡萄球菌（MRSA）临床分离株的活性。在虚拟筛选实验中，还将 chaxamycins A-D（1-4）对接进入 Hsp90 N 端结构域的 ATP 结合口袋中，并讨论了观察到的相互作用。
