Three genes encoding AfsK, AfsR, AfsS homologues in Streptomyces pristinaespiralis were studied, respectively, to investigate regulatory role of AfsKRS system for pristinamycin biosynthesis. Transcription change and gene inactivation analysis indicated that these genes had active transcription and positive regulation for the improvement of pristinamycin production in S. pristinaespiralis. The analysis of AfsKRS-defective mutagenesis indicated that there might be a positive correlation between the product of afsK and pristinamycin I biosynthesis, and a negative correlation to pristinamycin II biosynthesis. However, both afsR and afsS might have negative correlation to pristinamycin I production and positive correlation to pristinamycin II production. The effects on pristinamycin production of AfsKRS disruptants by protein kinase inhibitor K252a indicated that AfsR, both not AfsK and AfsS, was the inhibition target of K252a in S. pristinaespiralis, and AfsR should serve as a pleiotropic regulator to have differential regulation on biosynthesis of pristinamycin I and II components. Based on above study, it might be deduced that different signal transduction patterns via AfsK, AfsR, AfsS of AfsKRS system should be involved in respective regulation for biosynthesis of pristinamycin I and II in S. pristinaespiralis. In conclusion, the investigation could give some valuable clues for exploring furtherly regulatory function of AfsKRS system in S. pristinaespiralis.

分别研究了原始螺旋链霉菌中编码 AfsK、AfsR、AfsS 同源物的三个基因，以研究 AfsKRS 系统对原始霉素生物合成的调节作用。转录变化和基因失活分析表明，这些基因对提高原始螺旋体中原始霉素的产生具有积极的转录和正向调控作用。AfsKRS缺陷诱变分析表明，afsK的产物可能与原始霉素I生物合成呈正相关，与原始霉素II生物合成呈负相关。然而，afsR和afsS可能与原始霉素 I 的产生呈负相关，与原始霉素 II 的产生呈正相关。蛋白激酶抑制剂 K252a 对 AfsKRS 破坏物对原始霉素产生的影响表明，AfsR 不是 AfsK 和 AfsS，是S. pristinaespiralis中 K252a 的抑制目标，并且 AfsR 应作为多效性调节剂对原始霉素的生物合成进行差异调节I 和 II 组件。综合以上研究，可以推断，AfsKRS系统的AfsK、AfsR、AfsS的不同信号转导模式应该参与了对原原霉素I和II生物合成的调控。. 综上所述，本研究可为进一步探索 AfsKRS 系统在S. pristinaespiralis中的调控功能提供一些有价值的线索。