Zhou W, Holzhauer-Rieger K, Dors M, Schügerl K
Institut für Technische Chemie, Universität Hannover, Germany.
Enzyme Microb Technol. 1992 Oct;14(10):848-54. doi: 10.1016/0141-0229(92)90103-u.
Cephalosporin C was produced by a highly productive strain of Cephalosporium acremonium under industrial production conditions by fed-batch cultivation in a 40-l stirred-tank reactor using a complex medium containing 50 g l-1 peanut flour. The influence of dissolved oxygen concentration (pO2, DOC), which was maintained at different constant levels between 5 and 40% of its saturation value, during the production phase by means of a parameter-adaptive pO2-controller, on the cephalosporin C biosynthesis, was investigated. The concentrations of cephalosporin C (CPC) and its precursors penicillin N (PEN N), deacetoxycephalosporin C (DAOC), and deacetylcephalosporin C (DAC) were monitored by on-line HPLC. The concentrations of amino acids, valine (VAL), cysteine (CYS), alpha-amino-adipic acid (alpha-AAA), the dipeptide alpha-amino-adipyl-cysteine (AC), and the tripeptide alpha-amino-adipyl-cysteinyl-valine (ACV) were determined by off-line HPLC. By reducing the pO2 in the production phase from 40 to 5% of its saturation value, the CPC concentration diminished from 7.2 to 1.1 g l-1 and the PEN N concentration increased from 2.57 to 7.65 g l-1. The DAC concentration also dropped from 3.13 to 0.42 g l-1; however, the DAOC concentration was less influenced. The concentrations of AC and ACV were also less affected. The small DOC did not lead to an accumulation of the intermediate AC and ACV during the production phase. With increasing DOC in the range of 5-20%, the maximal specific production rate, the cell mass concentration-based and the substrate-based yield coefficients for CPC increased almost linearly, and fell back for PEN N.(ABSTRACT TRUNCATED AT 250 WORDS)
在工业生产条件下，使用含有50 g l-1花生粉的复合培养基，在40升搅拌罐反应器中通过补料分批培养，由一株高产顶头孢霉生产头孢菌素C。通过参数自适应pO2控制器在生产阶段将溶解氧浓度（pO2，DOC）维持在其饱和值的5%至40%之间的不同恒定水平，研究其对头孢菌素C生物合成的影响。通过在线高效液相色谱法监测头孢菌素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）的浓度。通过离线高效液相色谱法测定氨基酸、缬氨酸（VAL）、半胱氨酸（CYS）、α-氨基己二酸（α-AAA）、二肽α-氨基己二酰半胱氨酸（AC）和三肽α-氨基己二酰半胱氨酰缬氨酸（ACV）的浓度。通过将生产阶段的pO2从其饱和值的40%降至5%，CPC浓度从7.2 g l-1降至1.1 g l-1，PEN N浓度从2.57 g l-1增加到7.65 g l-1。DAC浓度也从3.13 g l-1降至0.42 g l-1；然而，DAOC浓度受影响较小。AC和ACV的浓度也受影响较小。在生产阶段，低DOC不会导致中间产物AC和ACV的积累。在5%-20%的范围内，随着DOC的增加，CPC的最大比生产速率、基于细胞质量浓度和基于底物的产率系数几乎呈线性增加，而PEN N则下降。（摘要截断于250字）
