Cephalosporin C production by a highly productive Cephalosporium acremonium strain in an airlift tower loop reactor with static mixers

Abstract

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.