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Rheological characterization of a fungal fermentation for the production of pneumocandins

机译:用于生产肺炎链菌素的真菌发酵的流变学表征

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The filamentous fungus Glarea lozoyensis produces a novel, pharmaceutically important pneumocandin (B_0) that is used to synthesize a polypeptide, which demonstrates fungicidal activity against clinically relevant pathogens. The scale-up of the pneumocandin fermentation requires an understanding of the rheological properties of the broth and the factors that influence flow behavior. A systematic approach for characterizing the rheological properties using a standard methodology is presented here. An appropriate rheometer was chosen and the eects of shear rate ramping, broth handling, creep and yield testing were examined. The fed-batch fermentation used a soluble production medium that allowed the relationship between biomass and rheological properties to be studied up to the 19-m~3 scale. The morphologically heterogeneous broth demonstrated time-dependent shear thinning behavior with thi-xotropy and a yield stress. The flow curves were described by the power law model, with flow behavior of 0.35-0.4 and consistency index up to 10 Pa.s~n. The use of a cup and bob rheometer was preferable to alternative techniques, including turbine and spindle systems defined by Mits-chka's technique. The consistency index and flow behavior were shown to have a non-linear relationship with biomass concentrations up to 1.40 g/L. The consistency index continually increased with biomass during the fermentation, while the flow behavior initially decreased rapidly and then remained at low values for the remainder of the batch cultivation. The consistency index and yield stress were influenced by temperature, osmotic pressure, and pH, while the flow behavior remained independent of these factors.
机译:丝状真菌Glarea lozoyensis产生了一种新型的,重要的,药学上重要的肺炎链菌素(P_0),用于合成多肽,该多肽对临床相关病原体具有杀真菌活性。肺炎链菌素发酵的规模化需要了解肉汤的流变特性以及影响流动行为的因素。本文介绍了使用标准方法表征流变性质的系统方法。选择合适的流变仪,并检查剪切速率斜升,肉汤处理,蠕变和屈服测试的效果。分批补料发酵使用可溶性生产培养基,该培养基允许研究生物量与流变性质之间的关系,直至19 m〜3规模。形态异质的肉汤表现出随时间变化的剪切变稀行为,具有触变性和屈服应力。用幂律模型描述了流动曲线,流动特性为0.35-0.4,稠度指数高达10 Pa.s〜n。比起其他技术(包括由Mits-chka技术定义的涡轮和主轴系统),杯子和鲍勃流变仪的使用更为可取。结果表明,稠度指数和流动行为与高达1.40 g / L的生物量浓度具有非线性关系。在发酵过程中,稠度指数随着生物量的增加而持续增加,而流动行为最初迅速下降,然后在其余的分批培养中保持较低的水平。稠度指数和屈服应力受温度,渗透压和pH值的影响,而流动行为却不受这些因素影响。

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