Influence of medium composition on the cephalosporin C production with a highly productive strain Cephalosporium acremonium

Abstract

Cephalosporin production by a highly productive Cephalosporium acremonium strain was carried out and optimized by fed-batch operation in a 40 l stirred tank reactor using a complex medium containing 30–120 g l −1 peanut flour. The concentrations of cephalosporin C (CPC) and its precursors: penicillin N (PEN N), deacetoxy cephalosporin C (DAOC), and deacetyl cephalosporin C (DAC) were monitored with an on-line HPLC. The concentrations of amino acids valine (VAL), cysteine (CYS), α-amino adipic acid (α-AAA), the dipeptide α-amino-adipyl-cysteine (AC), and the tripeptide α-amino-adipyl-cysteinyl-valine (ACV), were determined off-line by HPLC. The RNA content and dry weight of the sediment as well as the oxygen transfer rate (OTR) and the CO 2 production rate (CPR) were used to calculate the cell mass concentration ( X). The influences of peanut flour (PF) and the on-line monitored and controlled medium components: glucose (GLU), phosphate, methionine (MET) as well as the dissolved oxygen (DOC) on the cell growth, the product formation, and the pathway of cephalosporin C biosynthesis were investigated and evaluated. When the glucose fed-batch cycle was optimized and oxygen transfer limitation was avoided (DOC > 20% of the saturation value), high process performance (103.5 g l −1 X, 11.84 g l −1 CPC, a maximum CPC productivity of 118 mg l −1 h −1, and the whole concentration of the β-lactam antibiotics CPC, DAC, DAOC, PEN N 17.34 g l −1) was achieved by using 100 g l −1 PF in the medium with the optimum concentration of phosphate (260–270 mg l −1) and a low glucose concentration (< 0.5 g l −1). The cultivations with different medium concentrations demonstrated that the product formation was directly proportional to the cell mass concentration. On the average, the cell mass-based yield coefficient of CPC: Y CPC/X amounted to 0.115 g CPC per g cell mass.