基因工程FR-008/杀念菌素脱羧衍生物发酵过程优化

Optimization on culture process conditions for biosynthesis of novel FR-008/candicidin derivatives by a mutant of Streptomyces sp.

以组合生物合成技术得到的基因工程FR-008／杀念菌素脱羧衍生物CS103为研究对象，在摇瓶水平进行培养条件的初步优化。确定了接种量、接种时间、发酵过程pH、装液量等初步条件。对3.7L发酵罐水平的培养条件进行优化，确定了最适搅拌转速和通气量，并初步建立了补料分批发酵工艺。结果表明，接种时间30h、接种量为10％、控制pH6.5-7.0、搅拌转速450r／min、通气量200L／h，发酵过程维持发酵液残余葡萄糖浓度5g／L左右，在3.7L发酵罐基因工程FR-008／杀念菌素脱羧衍生物CS103产量达到99.87μg／ml。本研究为基因工程FR-008／杀念菌素工业化生产工艺提供了依据。

The novel derivatives of polyene macrolides antibiotic FR-008/candicidin with lower toxicity was conducted through combinatory biochemistry method. Firstly, several basic fermentation conditions were designed in shake flasks, such as inoculums age and size, broth volume and the pH of the fermentation process secondly, the further optimization of the culture conditions was performed in a 3.7 L fermentor, and the opti- mization strategy allowed the antibiotic production increased to 99.87μg/ml. This work made a stable theoretics for the fermentation scale-up process of the FR-008/candicidin derivatives with lower toxicity.