Collinone, a new recombinant angular polyketide antibiotic made by an engineered Streptomyces strain
Collinone, a new recombinant angular polyketide antibiotic made by an engineered Streptomyces strain
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DOI：
10.7164/antibiotics.54.239
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发表时间：
2001-03-01
影响因子：
3.3
通讯作者：
Minas, W
中科院分区：
文献类型：
--
作者：
Martin, R;Sterner, O;Minas, W
克隆了含有红霉素聚酮合成酶基因簇不同部分的大片段，并在天蓝色链霉菌CH999中进行了功能表达。这些克隆的表达产生了5种与柯林斯链霉菌培养提取物中未检测到的10种代谢物相似的代谢产物。本文重点研究了一种新的代谢物--柯林酮，它被大量分离和纯化，用于波谱结构测定和生物筛选。柯里酮是一种严重氧化的角状六环化合物，含有一种罕见的1，4，5，8(2H，3H)-蒽三酮部分，以前只有报道存在于从链霉菌中分离出来的抗生素SF2446A1、A2、A3、B1和B2中。SF2446。柯林酮的结构分析表明，它是一种碳链为26的十三酮化合物。柯林酮的基本苯环[a]环系是有棱角的，类似于著名的绞股蓝环素和血管环素抗生素的苷元。柯林酮对万古霉素耐药肠球菌有一定的抗菌活性。未检测到明显的抗真菌或抗病毒活性。通过进一步对其途径进行基因工程，可为获得新的具有生物活性的血管环素类化合物提供一个很好的起点。
Large chromosomal DNA fragments containing different parts of the putative rubromycin polyketide synthase gene cluster were cloned and functionally expressed in S. coelicolor CH999. Expression of these clones yielded 5 similar to 10 metabolites that were not detected in S. collinus culture extracts. This paper focusses on one of the new metabolites, termed collinone, that was isolated in large quantities and purified for spectroscopic structure determination and biological screening assays. Collinone is a heavily oxidized angular hexacyclic compound containing an unusual 1,4,5,8(2H,3H)-anthracenetetrone moiety previously only reported to be present in antibiotics SF2446A1, A2, A3, B1 and B2 isolated from Streptomyces sp. SF2446. Structure analysis of collinone indicates a tridecaketide with a 26 carbon backbone. The basic benz[a]naphthacene ring system of collinone is angular, similar to the aglycones of the well-known angucycline and angucyclinone antibiotics. While collinone showed antibacterial activity against vancomycin-resistant enterococci. no antifungal or significant antiviral activities were detected. Collinone could be a good starting point to obtain new bioactive angucyclin(on)e-like compounds by further genetic engineering of its pathway.