Study On The Nutrient Metabolism Network Mediated By Phosphate-Sensing Regulator In Actinomycetes

Microorganisms are the most changeable and adaptable organisms on Earth,especially bacteria,which have evolved a series of complex and precision signal transduction pathways to cope with and adapt to the changing external environments.Prokaryotic cells,such as actinomycetes,mainly use two-component signal systems mediated by histidine and aspartate phosphorylation to sense different signals in living conditions and rapidly transmit the signals into bacteria to initiate the transcription,translation and post-translational modifications of related genes,playing corresponding biological regulatory functions.In view of the fact that phosphorus is an essential element in organisms involved in central energy metabolism,post-translational modifications and synthesis of various substances,we have studied the important role and significance of phosphate sensing and metabolic processes in actinomycetes by representative research objects,Mycobacterium smegmatis and Saccharopolyspora erythraea.On the one hand,we found that the phosphate-sensing regulatory protein RegX3 is required for M.smegmatis to tolerate high concentration of short-chain fatty acid propionate.It can promote the methylcitrate cycle by activating PrpR regulator,and further change strain morphology to maintain their metabolic balance,growth and survival in the low phosphorus environment of macrophages.This study provides a potential drug target for the treatment of pathogenic actinomycetes like Mycobacterium tuberculosis.On the other hand,we analyzed the regulation of two S-adenosylmethionine?SAM?synthesis isoenzyme encoding genes by PhoP,a global regulator of phosphorus metabolism in S.erythraea.It was confirmed that PhoP directly induces the more important SAM synthase encoded by SACE₃900 and promotes SAM formation,providing sufficient methyl groups for the key step in erythromycin biosynthesis?the conversion of erythromycin C to erythromycin A?to improve the quality and yield of erythromycin.And the global nitrogen regulator,GlnR,has the same regulatory pattern with PhoP.It inspired a new way to increase the application value and economic benefit of industrial rare actinomycetes.