基因组信息指导的星海链霉菌中2-甲硫基-N6-(4-羟基异戊烯基)-腺苷的分离鉴定

Genome guided identification of 2-methylthio-N6-(4-hydroxy-isopentenyl)-adenosine from Streptomyces xinghaiensis NRRL B24674T

摘要:

[目的] 研究海洋链霉菌新种星海链霉菌Streptomyces xinghaiensis NRRL B24674^T次级代谢物中是否存在2-甲硫基-N⁶-异戊烯基修饰的腺苷。[方法] 通过生物信息学分析星海链霉菌S. xinghaiensis NRRL B24674^T基因组序列,寻找这类化合物的生物合成相关基因;采用正相硅胶柱色谱、反相硅胶柱色谱、凝胶柱色谱和高效液相色谱等分离技术对该菌株的发酵粗提物进行分离纯化;利用质谱与核磁共振等波谱技术鉴定化合物的结构。[结果] 在星海链霉菌基因组中找到含有2-甲硫基-N⁶-异戊烯基修饰的化合物生物合成途径中的2个同源蛋白;从该菌的发酵液中分离鉴定了2-甲硫基-N⁶-(4-羟基异戊烯基)-腺苷(ms²io⁶A)。[结论] 星海链霉菌S. xinghaiensis NRRL B24674^T存在此类腺苷修饰反应,并且是首次在链霉菌中发现此类腺苷修饰。生物信息学分析预示着链霉菌中可能普遍存在此类核酸或者核苷修饰。

Abstract:

[Objective] To investigate the production of adenosine modified with N⁶-(Δ²-isopentenyl) and 2-thiomethyl groups from marine-derived Streptomyces xinghaiensis NRRL B24674^T. [Methods] Bioinformatics analysis was carried out to search the genome sequence of S. xinghaiensis NRRL B24674^T and the secondary metabolites were purified by silica gel column chromatography, gel chromatography and high-performance liquid chromatography, and the chemical structure was elucidated by nuclear magnetic resonance (NMR) and mass spectroscopy (MS). [Results] Two proteins involved in such a biosynthetic pathway were found in the genome of S. xinghaiensis NRRL B24674^T; 2-methylthio-N⁶-(4-hydroxyisopentenyl)-adenosine has been purified from the liquid culture of S. xinghaiensis NRRL B24674^T, and its chemical structure was elucidated by analysis of high-resolution mass spectrometry (HR-MS) and NMR data. [Conclusion] Such an adenine modification process was present in S. xinghaiensis NRRL B24674^T, and it is the first time to report this kind of adenine modification from actinomycetes Streptomyces. Bioinformatics analysis implies that Streptomyces can also have this kind of RNA or adenine modification.