利福霉素B发酵过程中巴比妥钠加量的优化
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摘要：目的优化利福霉素发酵摇瓶中巴比妥钠的添加量及添加策略，以提高发酵产量。方法采用摇瓶发酵，优化巴比妥钠初始含量及中间补加策略，通过测定发酵液中利福霉素B的效价及菌体浓度来确定合适的发酵工艺。结果巴比妥钠添加的优化策略为：初始浓度0.05%，72 h补加至0.1%，120 h补加至0.15%。结论优化工艺使发酵单位显著提高，比不加巴比妥钠提高17%，比目前生产水平提高10%以上。
关键词：利福霉素；地中海拟无枝酸菌；巴比妥；发酵优化
中图分类号：R978.1+5文献标识码：A文章编号：1672-979X(2007)02-0011-03
Optimization of Barbital Sodium Content during Fermentation of Rifamycin B
WANG Jun-feng1, DU Ji-quan2
(1.Shenyang Tonglian Pharmacy Group, Institute of Biological Technology of Shanghai, Shanghai 200237, China; 2. Management Committee of Jinan High & New Technology Developing Zone, Jinan 250002, China)
Abstract：Objective To optimize the content and feeding strategy of barbital sodium during the fermentation of rifamycin B in order to improve the yield. Methods In shaken flask culture, the content and feeding strategy of barbital sodium during the fermentation of rifamycin B was optimized and the suitable fermentation technology was also defined by determining the potency of rifamycin B and PMV of mycelia in fermentation broth. ResultsThe optimal feeding strategy of barbital sodium was obtained, which was that the incipient concentration of barbital sodium was 0.05% in base medium and was added to 0.1% at 72 h, 0.15% at 120 h. Conclusion The yield of rifamycin B is raised significantly with the technology optimized. The productivity of rifamycin B is increased by 17% than that without barbital sodium and 10% more than that produced at the present level.
Key words：rifamycin B; Amycolatopsis mediterranei; barbital; fermentation optimization
利福霉素(rifamycin)是地中海拟无枝酸菌(Amycolatopsis mediterranei)产生的一类安莎(ansamycin)大环内酯抗生素，广泛用于治疗革兰阳性菌(G+)、结核病、麻风病以及与艾滋病有关的分枝杆菌感染[1]。近年分枝杆菌引起的肺结核患者数量呈上升趋势，因此研究利福霉素及其产生菌有重要意义。
从地中海拟无枝酸菌培养液中得到的利福霉素有A，B，C，D，E5种组分，其中主要为B。后来在不同菌种的发酵液中又发现了O，S，SV组分[2, 3]。
利福霉素B只有微弱的抑菌活性，但是，它可以通过化学修饰、酶催化或生物转化成为抑菌活性较高的SV。SV是首个临床应用的利福霉素类抗生素。SV是B生物合成的前体，阻断B合成的菌株可导致SV积累，此方案已经成功地实施[4]，但是经过处理的菌株产量较低。目前商业应用大多先生产B，然后将其转化为O，S及SV，转化关系如图1所示[5]。
图1 利福霉素B转化为利福霉素SV和其他临床应用的类似物
巴比妥(barbital)能够刺激A. mediterranei合成利福霉素 ......
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