Abstract：
Ansamycins, represented by the antituberculosis drug rifamycin, are an important family of natural products. To obtain new ansamycins, Streptomyces rapamycinicus IMET 43975 harboring an ansamycin biosynthetic gene cluster was fermented in a 50 L scale, and subsequent purification work led to the isolation of five known and four new analogues, where hygrocin W (2) belongs to benzoquinonoid ansamycins, and the other three hygrocins, hygrocins X-Z (6-8), are new seco-hygrocins. The structures of ansamycins (1-8) were determined by the analysis of spectroscopic (1D/2D NMR and ECD) and MS spectrometric data. The Baeyer-Villiger enzyme which catalyzed the ester formation in the ansa-ring was confirmed through in vivo CRISPR base editing. The discovery of these compounds further enriches the structural diversity of ansamycins.
摘要：
安莎霉素,以抗结核药物利福霉素为代表，是天然产品的重要家族。为了获得新的安莎霉素，含有安莎霉素生物合成基因簇的雷帕霉素链霉菌IMET43975在50L规模内发酵，随后的纯化工作导致了五个已知的和四个新的类似物的分离，其中hygrocinW(2)属于苯醌类安莎霉素，还有另外三种潮霉素,hygrocinsX-Z(6-8),是新的Seco-hygrocins.通过光谱分析(1D/2DNMR和ECD)和MS光谱数据确定安莎霉素(1-8)的结构。通过体内CRISPR碱基编辑证实了催化柄环中酯形成的Baeyer-Villiger酶。这些化合物的发现进一步丰富了安莎霉素的结构多样性。
