Two-component systems(TCSs)play important roles in the regulation of secondary metabolism in Streptomyces.However,so far,few TCSs have been functionally identified in the rapamycin-producing strain,Streptomyces rapamy...Two-component systems(TCSs)play important roles in the regulation of secondary metabolism in Streptomyces.However,so far,few TCSs have been functionally identified in the rapamycin-producing strain,Streptomyces rapamycinicus.In this study,a two-component system(TCS)CseB-C(M271_22640/M271_22645)in S.rapamycinicus NRRL 5491,whose homolog from Streptomyces coelicolor is involved in regulating cell wall integrity and secondary metabolism,was identified to play a dual role in differential regulation of antibiotic biosynthesis,activating rapamycin biosynthesis and simultaneously repressing elaiophylin biosynthesis.We showed that knockout of cseB-C resulted in a drastic reduction in rapamycin production and a significant increase in elaiophylin production.Transcriptional analysis revealed that deletion of cseB-C resulted in a substantial decrease in the transcription of sigE,which clusters together with cseB-C.Introduction of sigE into theΔcseB-C mutant could fully restore rapamycin and elaiophylin production to the wild-type levels,suggesting that the role of CseB-C on rapamycin and elaiophylin biosynthesis is mediated by sigE.Collectively,the results obtained in this study contribute to a better understanding of the regulation of rapamycin and elaiophylin biosynthesis in S.rapamycinicus.展开更多
基金supported by the Key Research and Development Project of Henan Province(Grant Number 241111111200,231111310700)Open Project Program of National Engineering Research Center of Wheat and Corn Further Processing,Henan University of Technology(Grant Number NL2024004)+2 种基金China Postdoctoral Science Foundation(Grant Number 2024M760793)Natural Science Foundation of Henan(Grant Number 242300421557)National Natural Science Foundation of China(Grant Number 32270095).
文摘Two-component systems(TCSs)play important roles in the regulation of secondary metabolism in Streptomyces.However,so far,few TCSs have been functionally identified in the rapamycin-producing strain,Streptomyces rapamycinicus.In this study,a two-component system(TCS)CseB-C(M271_22640/M271_22645)in S.rapamycinicus NRRL 5491,whose homolog from Streptomyces coelicolor is involved in regulating cell wall integrity and secondary metabolism,was identified to play a dual role in differential regulation of antibiotic biosynthesis,activating rapamycin biosynthesis and simultaneously repressing elaiophylin biosynthesis.We showed that knockout of cseB-C resulted in a drastic reduction in rapamycin production and a significant increase in elaiophylin production.Transcriptional analysis revealed that deletion of cseB-C resulted in a substantial decrease in the transcription of sigE,which clusters together with cseB-C.Introduction of sigE into theΔcseB-C mutant could fully restore rapamycin and elaiophylin production to the wild-type levels,suggesting that the role of CseB-C on rapamycin and elaiophylin biosynthesis is mediated by sigE.Collectively,the results obtained in this study contribute to a better understanding of the regulation of rapamycin and elaiophylin biosynthesis in S.rapamycinicus.
