Improved large-scale production of Daptomycin by Streptomyces roseosporus M1208 with Caprate

来源 :2012工业生物过程优化与控制研讨会 | 被引量 : 0次 | 上传用户:liongliong470
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  Daptomycin is known to act by disrupting multiple aspects of bacterial cell membrane function,and it is useful against skin infections caused by multi-resistant Gram-positive bacteria and it has relatively minor side effects.Streptomyces roseosporus are fed decanoic acid as a precursor during fermentation to selectively produce daptomycin and increase its yield.The presence of the solvent in the feeding solution is necessary,because decanoic acid is a waxy solid at least 50% solvent are sufficiently fluid to be fed.However,even in the presence of a solvent,at temperatures lower that 25 ℃,it is diffucult to maintain a constant and homogeneous feeding,because decanoic acid may seperate from the solution.And decanoic acid is highly toxic,microbes can die from overdose of this precursor,so the feeding rate must be kept under strict control.In this paper we use alternative sources of the n-decanoyl side-chain,namely caprate(Sodium Caprate,Potassium caprate,Ammonium Caprate).These reagents allow to ruduce toxicity effects on the bacteria and avoid the use of solvents in the feeding solution.The results obtained in shake-flask experiments demonstrated that caprate could greatly stimulate daptomycin biosynthesis.And than an efficient and economical control strategy of caprate was established for daptomycin production in a 10-m3 fermenter,in which caprate was continuously fed to maintain decanoic acid concentration of the broth at the range of 50-100ppm during 24-180h of fermentation,and in the end of fermentation the concentration of daptomycin reached 2000mg/L.
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