Double bond shifts and biosynthetic mega-complex analysis of vancoresmycin (B07)

将继续进行万古霉素（一种高效细菌聚酮化合物）的病例研究。天然产物和设计的类似物将通过定向全合成来制备，以研究特征性双键移位的机制及其对生产菌株的细胞影响。我们还将研究它们对抗生素活性和细胞壁生物合成的影响。将首次分配万古霉素的完整3D结构，这将澄清大基因簇的矛盾生物合成分析以及某些立体化学测定的计算机模拟方法的一般可靠性。

A case study with vancoresmycin, a highly potent bacterial polyketide, will be pursued. The natural product and designed analogs will be prepared by directed total syntheses to investigate the mechanisms of characteristic double bond shifts and their cellular impact on the producer strain. We will also study their effect on antibiotic activity and cell wall biosynthesis. The full 3D structure of vancoresmycin will be assigned for the first time, which will clarify contradictory biosynthetic analyses of the mega gene cluster as well as the general reliability of certain in silico methods for stereochemical determination.