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目的在吸水链霉菌17997格尔德霉素生物合成PKS后修饰gdmN-变株发酵产物中寻找新格尔德霉素衍生物。方法 gdmN-变株发酵上清液乙酸乙酯提取后,进行硅胶板TLC分析;对一个红色目标化合物进行了HPLC和高分辨质谱分析,并对其进行了1H-和13C-核磁共振(NMR)分析;对红色目标化合物在吸水链霉菌17997格尔德霉素PKS基因阻断变株中进行了生物转化实验。结果在gdmN-变株发酵产物中发现了1个预期的红色目标化合物(4,5-双氢-7-去氨甲酰基-7-羟基-19-S-甲基格尔德霉素);该目标化合物可被格尔德霉素生物合成PKS后修饰系统7-O-氨甲酰化,生成4,5-双氢-19-S-甲基格尔德霉素。结论在gdmN-变株中发现了4,5-双氢-7-去氨甲酰基-7-羟基-19-S-甲基格尔德霉素;该化合物可被格尔德霉素PKS后修饰系统继续7-O-氨甲酰化,但不能C-4,5氧化。
OBJECTIVE: To search for new geldanamycin derivatives in fermentation products of gdmN-mutants after S. hygroscopicus 17997 geldanamycin biosynthesizes PKS. Methods After the gdmN-variant fermentation broth was extracted with ethyl acetate, TLC analysis was carried out on a silica gel plate. A red target compound was characterized by HPLC and high resolution mass spectrometry. 1H- and 13C-NMR spectra were obtained. The biotransformation experiment was carried out on the red target compound in the Streptomyces hygroscopicus 17997 geldanamycin PKS gene mutant strain. As a result, one expected red target compound (4,5-dihydro-7-decarbamyl-7-hydroxy-19-S-methylgeldanamycin) was found in the fermentation product of gdmN- The target compound can be carbamoylated by the geldanamycin biosynthesis PKS post-modification system 7-O-carbamylated to 4,5-dihydro-19-S-methylgeldanamycin. CONCLUSIONS 4,5-Dihydro-7-decarbamyl-7-hydroxy-19-S-methylgeldanamycin was found in the gdmN-mutant; this compound can be used after geldanamycin PKS The modification system continues with 7-O-carbamylation, but not C-4,5 oxidation.