微粒添加对棘白菌素B发酵过程的影响

Effect of microparticles on echinocandin B production by Aspergillus nidulans

摘要:

阿尼芬净是一种新型的抗真菌药物，能够抑制各种致病念珠菌在活体内外的活性。棘白菌素B (Echinocandin B，ECB) 是合成阿尼芬净的关键前体，其发酵单位的高低直接关系到阿尼芬净的价格及市场前景。文中考察了巢曲霉在摇瓶发酵生产ECB的过程中，添加滑石粉、Al2O3、玻璃珠等微粒对其发酵单位的影响。发现微粒的粒径和添加浓度是菌体形态和ECB产量的关键影响因素，添加20 g/L滑石粉 (d50 = 14.2 μm) 和7颗玻璃珠 (d = 6 mm) 可使ECB发酵产量分别比对照提高33.2%和41.7%，达到1 262.9 mg/L和1 344.1 mg/L。结果表明微粒的添加可以显著地改善丝状微生物发酵过程中的菌丝形态，提高其产物的发酵产量，为丝状微生物发酵过程的优化提供了一种重要手段。

Abstract:

Anidulafungin is an effective antifungal medicine, which can inhibit activities of candida in vitro and in vivo. Echinocandin B (ECB) is the key precursor of Anidulafungin, thus the price and market prospect of Anidulafungin is directly due to the fermentation titer of ECB. In this study, Aspergillus nidulans was used for ECB fermentation, and the influence of adding microparticles on ECB fermentation was studied, such as talcum powder, Al2O3, and glass beads. The particle size and concentration were the key factors for mycelium morphology and ECB production, and ECB production could reach 1263 mg/L and 1 344 mg/L by adding talcum powder of 20 g/L (d50 = 14.2 μm) and 7 glass beads (6 mm), an increase by 33.2% and 41.7%, respectively. The results indicated that the mycelium morphology of filamentous microorganisms and the product yield of fermentation could be improved by adding microparticles remarkably, and it provide an important method for the fermentative optimization of filamentous microorganisms.