Zhou W, Holzhauer-Rieger K, Bayer T, Schügerl K
Institut für Technische Chemie, Universität Hannover, Germany.
J Biotechnol. 1993 Apr;28(2-3):165-77. doi: 10.1016/0168-1656(93)90168-m.
The production of cephalosporin C (CPC) and its precursors penicillin N (PEN N), deacetoxycephalosporin C (DAOC) and deacetylcephalosporin C (DAC), with a highly productive strain of Cephalosporin acremonium, was investigated in an 80-1 airlift tower loop reactor with four static mixer modules (Type SMV, Sulzer) (ATLRM) on a complex medium containing 50 g l-1 peanut flour (PF). The most important key parameters such as glucose concentration and cell mass concentration were monitored during a fed-batch cultivation process. The concentrations of products CPC, PEN N, DAOC an DAC were determined on line by HPLC. The influences of four motionless mixers on the dissolved oxygen concentration (DOC), oxygen transfer rate, the cell growth and the CPC production, as well as the reactor performance, were evaluated. The results were compared with the performance of an airlift tower loop reactor (ATLR) without static mixers as well as with a stirred tank reactor (STR). A comparison of cultivations in the ATLRM and ATLR with 50 g l-1 PF indicates that the obtained maximal CPC concentration and the (CPC + DAC + DAOC) concentration were 7% and 22% higher in the ATLRM (4.96 and 7.46 g l-1) than in the ATLR (4.63 and 6.13 g l-1) respectively. The maximal CPC volumetric productivity in the ATLRM (55.1 mg l-1 h-1) was also considerably higher than that in the ATLR (48.5 mg l-1 h-1). The specific power input was reduced from 2.36 to 1.5 kW m-3, the specific productivity pertaining to the power input was improved from 1.96 to 3.31 g W-1. On the other hand, cultivation in the ATLRM had a lower maximum CPC concentration and volumetric productivity than those in STR (7.2 g l-1 and 71.2 mg l-1 h-1) with the same medium due to the lower shear stress levels and the lower specific power input (1.5 vs. 3.0 kW m-3); but the specific power imput-based yield coefficient was in the ATLRM (3.31 g W-1) higher than in the STR (2.40 g W-1). By increasing the amount of PF, it was possible to enhance the CPC concentration and volumetric productivity in the STR. However, the performance of the ATLRM was limited to using a medium containing maximal 50 g l-1 PF because of the high viscosity of the medium, the limited energy input and thus the limited oxygen supply.
在一个装有四个静态混合器模块（SMV型，苏尔寿公司）的80升气升式塔式环流反应器（ATLRM）中，以含有50 g l-1花生粉（PF）的复合培养基，对高产顶头孢霉菌株生产头孢菌素C（CPC）及其前体青霉素N（PEN N）、去乙酰氧基头孢菌素C（DAOC）和去乙酰头孢菌素C（DAC）进行了研究。在补料分批培养过程中，监测了葡萄糖浓度和细胞质量浓度等最重要的关键参数。通过高效液相色谱法在线测定产品CPC、PEN N、DAOC和DAC的浓度。评估了四个静态混合器对溶解氧浓度（DOC）、氧传递速率、细胞生长和CPC生产以及反应器性能的影响。将结果与无静态混合器的气升式塔式环流反应器（ATLR）以及搅拌罐反应器（STR）的性能进行了比较。在含有50 g l-1 PF的情况下，ATLRM和ATLR中的培养比较表明，ATLRM中获得的最大CPC浓度和（CPC + DAC + DAOC）浓度分别比ATLR中高7%和22%（分别为4.96和7.46 g l-1，以及4.63和6.13 g l-1）。ATLRM中的最大CPC体积生产率（55.1 mg l-1 h-1）也显著高于ATLR中的（48.5 mg l-1 h-1）。比功率输入从2.36降低到1.5 kW m-3，与功率输入相关的比生产率从1.96提高到3.31 g W-1。另一方面，由于较低剪应力水平和较低比功率输入（1.5对3.0 kW m-3），在相同培养基中，ATLRM中的培养最大CPC浓度和体积生产率低于STR中的（分别为7.2 g l-1和71.2 mg l-1 h-1）；但基于比功率输入的产率系数在ATLRM中（3.31 g W-1）高于STR中（2.40 g W-1）。通过增加PF的量，可以提高STR中的CPC浓度和体积生产率。然而，由于培养基的高粘度、有限的能量输入以及因此有限的氧气供应，ATLRM的性能仅限于使用最大含有50 g l-1 PF的培养基。
