Functional dissection of transport processes during glycopeptide antibiotic production (B02)

天然化合物的细菌生物合成基因簇-如抗生素-主要编码所产生化合物的输出者。拟无枝酸菌balhimycina，生产商的糖肽抗生素balhimycin，编码的ABC出口商Tba，这是至关重要的balhimycin分泌，但不是生产菌株的自身耐药性。在这里，我们希望进一步表征Tba在巴利霉素生产中的作用，并评估其对糖肽类抗生素的特异性。我们将采用一种综合方法，使用细菌遗传学，次级代谢产物的靶向分析，蛋白质定位，蛋白质-蛋白质相互作用分析以及体外转运试验。

Bacterial biosynthetic gene clusters of natural compounds – like antibiotics – mostly encode exporters of the compounds produced. Amycolatopsis balhimycina, producer of the glycopeptide antibiotic balhimycin, encodes the ABC exporter Tba, which was shown to be critical for balhimycin secretion but not for self-resistance of the producer strain. Here, we want to further characterize the role of Tba in balhimycin production and assess its specificity towards glycopeptide antibiotics. We will employ an integrated approach using bacterial genetics, targeted analysis of secondary metabolites, protein localization, and protein-protein interaction analysis as well as in vitro transport assays.