Study On Metabolic Responses To Exogenous Fe(?) And Mg(?) Of Streptomyces Hygroscopicus

Streptomyces hygroscopicus ATCC29253 produces four polyketide antibiotics,including rapamycin,elaiophylin,nigericin and hygrocins.Among them,Rapamycin and Hygrocin A could be expressed simultaneously under the same culture conditions.Exogenous Fe(?)and Mg(?)had a great effect on Rapamycin and Hygrocin A production in the fermentation of Streptomyces hygroscopicus ATCC 29253,and it is interesting to note that the effect of Fe(?)and Mg(?)on the yield of these two antibiotics is just the opposite.In this study,metabolomic analyses was employed to understand the responses of S.hygroscopicus to exogenous Fe(?)and Mg(?).The mechanism of Fe(?)and Mg(?)affecting the synthesis of Rapamycin and Hygrocin A was revealed,and the possible relationship of the simultaneous expression of Rapamycin and Hygrocin A on the metabolic network was also discussed.The main results were displayed as follows:1)In the fermentation process of S.hygroscopicus,the exogenous Fe(?)promoted the yield of Rapamycin and decreased the yield of Hygrocin A.A total of 53 metabolites in S.hygroscopicus were quantitatively identified with LC-QTOF-MS.In addition,10 potential biomarkers affecting Rapaycin production were identified by PCA and PLS analysis,including proline,phenylalanine,tyrosine,glutamic acid,arginine,lysine,serine,oleic acid.The exogenous Fe(?)affected the synthesis of intracellular fatty acids and amino acids of S.hygroscopicus to a certain extent and promoted the synthesis of Rapamycin.2)On the fermentation process of S.hygroscopicus,the exogenous Mg(?)promoted the yield of Hygrocin A and decreased the yield of Rapamycin.A total of 74 metabolites in S.hygroscopicus were quantitatively identified with LC-QTOF-MS.In addition,8potential biomarkers affecting Rapaycin production were identified by PCA and PLS analysis,including proline,phenylalanine,tryptophan,glutamic acid,arginine,lysine,serine,oleic acid,these metabolites mainly involve Proline,phenylalanine,tryptophan,tyrosine,arginine,lysine,serine,oleic acid.The effect of exogenous Mg(?)on amino acid metabolism of S.hygroscopicus was significant and promoted the synthesis of Hygrocin A.3)Based on the analysis of the metabolic differences of Exogenous Fe(?)and Mg(?)to Streptomyces hygroscopicus,it was found that the metabolic changes caused by the two metal ions were mainly reflected in the significant difference between amino acid metabolism and fatty acid metabolism.The effect of phenylalanine,tyrosine,oleic acid on the synthesis of Hygromycin A and Rapamycin was just the opposite.The results showed that there were different responses and regulation mechanisms of S.hygroscopicus to different metal ions,and also showed differences in the expression of two antibiotics.The above study explored the effects of exogenous Fe(?)and Mg(?)on the expression of antibiotics and metabolism responses of S hygroscopicus by metabolomics.The result on the one hand can provide a reasonable guide for the antibiotics production from S.hygroscopicus,on the other hand can provide research basis for the metabolic regulation research for simultaneous expression of multiple antibiotics...