A New Approach for Engineering Polyketides by Cytochrome P450 C-H Oxidation

在此输入文本，它是您的应用程序的新摘要信息。此部分必须为no 超过30行的文本。 由于出现了抗药性细菌(如 如耐甲氧西林金黄色葡萄球菌(MRSA) 迫切需要开发新的抗菌剂。 Kibdelmycin是一种新近发现的杂交聚酮/非... 核糖体多肽天然产物的分离 Kibdelosporangium sp.具有广谱的MA7385 对革兰氏阴性杆菌和革兰氏阴性杆菌的抑菌活性 阳性菌(包括耐甲氧西林金黄色葡萄球菌)。有趣的是， 这种新型抗生素的分子结构中含有许多 不寻常的官能团(例如，外环烯烃、 (二氯吡咯部分等)哪些项目提供了机会 用于修饰以提高其治疗性能。我们 正在努力生产新的衍生品 通过半合成和最终通过 前体导向的生物合成。为了实现这一目标 吉伯德霉素前体定向生物合成的目标 将通过以下方式鉴定吉伯德霉素的基因簇 Kibdelosporangium sp.的基因组分析MA7385。一次 我们已经确定了基因簇，我们将进行异源 该簇在大肠杆菌中的表达及关键字的研究 庆大霉素参与的生物合成转化 生物合成(例如，我们将研究生物合成 二氯吡咯部分，还确定是否 非天然的吡咯底物可以被结合到 天然产物)。通过这些结合的方法，我们的目标是 是为了生产一个小型的吉伯德霉素类似物文库，用于 作为抑菌剂的评价。

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Due to the emergence of antibiotic resistant bacteria (such as methicillin-resistant Staphylococcus aureus, MRSA) there is an urgent need to develop new antibacterial agents. Kibdelomycin is a recently discovered hybrid polyketide/non- ribosomal peptide natural product isolated from Kibdelosporangium sp. MA7385 that has broad spectrum bacteriostatic activity against both Gram negative and Gram positive bacteria (including MRSA). Intriguingly, the molecular structure of this new antibiotic contains many unusual functional groups (e.g. an exocyclic olefin, a dichloropyrrole moiety, etc.) which present opportunities for modification to improve its therapeutic properties. We are undertaking an effort to produce new derivatives of kibdelomycin through semi-synthesis and eventually by precursor directed biosynthesis. In order to realize the goal of precursor directed biosynthesis of kibdelomycin, we will identify the gene cluster of kibdelomycin through analysis of the genome of Kibdelosporangium sp. MA7385. Once we have identified the gene cluster, we will heterologously express the cluster in E. coli and study the key biosynthetic transformations involved in kibdelomycin biosynthesis (for example, we will study the biosynthesis of the dichloropyrrole moiety and also determine whether unnatural pyrrole substrates can be incorporated into the natural product). Through these combined approaches our aim is to produce a small library of kibdelomycin analogs for evaluation as bacteriostatic agents.