The Influence Of Metabolic Regulation On The Polymyxin E Synthesis

Polymyxin E is a multi-component alkaline polypeptide antibiotic produced by Paenibacillus polymyxa,used in the treatment of multi-drug resistant gram-negative infection.The aim of this thesis is to improve the polymyxin E yield by the optimization of fermentation medium,the study of the the mechanism of corn starch stimulating polymyxin synthesis and exploring the influence of polymyxin E fermentation regulation process in 5L fermemter.Compared with glucose,soluble starch is the optimal carbon source,which contributes to improve the yield of polymyxin E by 111%.CaCO₃,FeSO₄?7H₂O and MgSO₄ was the appropriate inorganic salts in the polymyxin E fermentation.The optimal medium composition was determined by Plackeet-Burman design and response surface method for polymyxin E production.The polymyxin E production was increased by15.1%using the optimized medium.The functional mechanism of stimulative factor in polymyxin E synthetic was studied.The results indicated that different ratios of glucose and corn starch on the growth of Paenibacillus polymyxa and the production of polymyxin E varied significantly.Corn starch was conducive to the transcriptional intensity of amylase,polymyxin synthetic genes?pmxA,pmxB,pmxC,pmxD,pmxE?and the positive regulation gene?spo0A?.The negative regulation gene?abrB?was been suppressed.In addition,polymyxin E would be biosynthesized efficiently when the proportion of glucose and corn starch was adjusted to 5:40.Polymyxin E fermentation processes were studied in the 5L fermenter using 5%glucose and 40%corn starch as a composite carbon source.The regulation of polymyxin E synthesis process was explored by adding corn starch hydrolysate in the 5L fermenter.The relative potency of polymyxin E was 2.88 times than that of the batch fermentation.