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Screening Strains And Optimization Of Culture For Clavulanic Acid Production

Posted on:2007-10-18Degree:MasterType:Thesis
Country:ChinaCandidate:Y F ShiFull Text:PDF
GTID:2121360185484684Subject:Pharmaceutical Engineering
Abstract/Summary:PDF Full Text Request
Based on the biosynthesis pathway and metabolic mechanism, rational selection was performed to obtain a clavulanic acid high-producing strain Streptomyces clavuligerus. Rational screening was adopted to select mutants which could grow well on the medium with high concentration of 14 % glycerol, 0.5 % K2HPO4 and 1.5 % sodium sulbactain. By above methods, an over-producing strain XC-CA-7-19 was screened out. The productivity of this strain reaches 1500 μg/mL, which is increased by 545 % compared with the parent strain XC-CA-1-26. The study on its hereditary character shows that this strain not only subculture stably, that is the high productivity character could be inherit stably, but also has the active glycerol transport system (GTS) which is specifically induced by glycerol and could efficiently transfer glycerol to clavulanic acid. Some materials which have inhibitive effects on GTS, such as L-serine, iodoacetate, fatty acids, can inhibit the biosynthesis of clavulanic acid and reduce the productivity.With the mutant strain XC-CA-7-19 as parent strain, the seed and fermentation medium was optimized for industrial production. On the above base, the effects of initial pH of the medium, seed age, inoculation volume, temperature, dissolved oxygen, shearing strength and precursors were...
Keywords/Search Tags:Clavulanic acid, Streptomyces clavuligerus, rational selection, glycerol tolerant mutant, phosphate tolerant mutant, sodium sulbactain resistant mutant, fermentation process optimization, precursor
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