癸酸抗性突变株流加发酵法生产达托霉素

Fed-Batch Fermentative Production of Daptomycin by Decanoic Acid Resistance Mutant

采用He-Ne激光对达托霉素产生菌玫瑰孢链霉菌LC-54进行诱变,筛选前体癸酸抗性突变株,在此基础上进一步考察了一次补料、间歇补料和恒速流加补料等不同补料策略对达托霉素发酵生产的影响．结果表明,选育前体癸酸抗性突变株可以提高达托霉素的生产能力,并最终获得了达托霉素发酵效价较出发菌株提高了37．2%的高产突变株LC-KS-54．采用恒速流加策略,能够有效地提高达托霉素产量,经过130 h的恒速流加培养,细胞干重达到15．4g/L,达托霉素产量达到258 mg/L,明显优于其他前体补料策略．

To select precursor decanoic acid resistance mutant, the parent strain Streptomyces roseosporus LC-54 was irradiated by He-Ne laser. Furthermore effects of different feeding strategies, including single feeding, fedbatch feeding and constant rate feeding, on daptomycin batch fermentations were studied by this mutan with decanoic acid as precursor. It is shown that screening precursor decanoic acid resistance mutant can improve the productivity of daptomycin. As a result, a daptomycin high-yielding mutant LC-KS-54 with the productivity increased by 37.2% than the parent strain was obtained. The results indicate that constant rate feeding can effec- tively improve the production of daptomycin in the fermentation process. The production of daptomycin reaches 258 mg/L with maximum cell mass of 15.4 g/L at the culture time of 130 h by constant rate feeding, which is obviously better than that of other feeding strategies