芽孢杆菌(Bacillus sp.)脂肽抗生素发酵工艺及分离纯化

微生物脂肽具有抗菌谱广、热稳定性高、低毒、低抗药性等优点,近年来受到国内外广泛关注。综述了芽孢杆菌脂肽抗生素的发酵和分离纯化工艺的最新研究进展。在发酵工艺中,培养基营养组成、发酵温度、搅拌转速和通气量等参数对脂肽的产量至关重要,碳源、氮源和金属离子的组成与配比都会影响芽孢杆菌的生长与产物的合成,适当控制搅拌转速和通气量可提高脂肽产量。此外,近年来一些新型发酵工艺,如泡沫回流、固定化细胞、无泡发酵、固态发酵等被用于脂肽生产,通过改进发酵方式,在降低成本的同时提高了脂肽抗生素产量。抗菌脂肽分离纯化的主要方法包括超滤、吸附、泡沫分离及色谱法等,这些方法相对于传统的酸沉和萃取,具有可连续生产、脂肽提取量高及成本低等优点。同时,多种纯化方法的组合应用大幅度提高了抗菌脂肽的提取效果,有效降低了成本,是脂肽抗生素分离提取的发展方向。

Current State in Fermentation, Isolation, and Purification of Lipopeptide Antibiotics from Bacillus sp.

Microbial lipopeptide has the advantages of better thermostability, lower toxicity, lower antibiotic resistance, and a broader antimicrobial spectrum, therefore, have aroused great concern at home and abroad in recent years. The advanced development in fermentation, isolation and purification of lipopeptide antibiotics productivity from Bacillus sp. has been reviewed. In the fermentation process of lipopeptide, the effects of medium nutrition composition, process parameters like temperature, agitation rate and ventilation are critical for the lipopeptide yield. The composition of carbon source, nitrogen source and metal ion have a significant effect on the growth of Bacillus sp. and the product synthesis. High lipopeptide yield can be obtained by controlling agitation rate and ventilation. Furthermore, new fermentative technology, such as bubbleless fermentation, foam recycling fermentation, cell immobilized fermentation and solid state fermentation, have been applied to the producing process of lipopeptide recently. By improving these new methods, lipopeptide yield is greatly enhanced meanwhile the cost is reduced. Isolation and purification of lipopeptide include ultrafiltration, adsorption, foam separation and chromatographic purification. These methods are available for continuous production, and have higher extraction rate as well as lower cost compared to traditional methods like acid precipitation and extraction. By the combination of different purification methods, lipopeptide extraction amounts were largely increased while the cost is reduced effectively which emerges a good development prospect in the future.