4,5-双氢-7-去氨甲酰基-7-羟基-19-S-甲基格尔德霉素及其与格尔德霉素生物合成PKS后修饰的关系

摘要

Objective To search for novel geldanmycin derivative(s) from the gdmN- mutant of Streptomyces hygroscopicus 17997. Methods The fermentation supernatant of gdmN- mutant was extracted with ethylacetate, and then separated by silica gel TLC. An expected red compound of interest was analyzed by HPLC and HR-ESI(+)-MS. The red compound was then purified for further 1H- and 13C- NMR confirmation. Byconversion of the red compound was performed in a geldanamycin polyketide synthase gene disruption mutant of Streptomyces hygroscopicus 17997. Results The expected red compound was identified as 4,5-dihydro-7-descarbomoyl-7-hydroxy-19-iS1-methylgeldanamycin. It could be bioconverted to 4,5-dihydro-19-S-methylgeldanamycin. Conclusion A novel geldanamycin derivative, 4,5-dihydro-7-descarbomoyl-7-hydroxy-19-1S'-methylgeldanamycin, was characterized in the gdmN' mutant of Streptomyces hygroscopicus 17997. 19-S-methylation of 4,5-dihydro-7-descarbomoyl-7-hydroxygeldanamycin does not interfere its carbamoylation, but blocks its C4,5-oxidation by the post-PKS tailoring process of geldanamycin biosynthesis.%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.