Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain

The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the content of endogenous polyamines increased by four- to five-fold. Other studies have shown that the addition of exogenous polyamines can increase the production of target secondary metabolites in highly active fungal producers, in particular, increase the biosynthesis of β-lactams in the Penicillium chrysogenum Wis 54–1255 strain, an improved producer of penicillin G. In the current study, we demonstrate that the introduction of exogenous polyamines, such as spermidine or 1,3-diaminopropane, to A. chrysogenum wild-type (WT) and HY strains, leads to an increase in colony germination and morphological changes in a complete agar medium. The addition of 5 mM polyamines during fermentation increases the production of cephalosporin C in the A. chrysogenum HY strain by 15–20% and upregulates genes belonging to the beta-lactam biosynthetic cluster. The data obtained indicate the intersection of the metabolisms of polyamines and beta-lactams in A. chrysogenum and are important for the construction of improved producers of secondary metabolites in filamentous fungi.

Modelling, optimization and control of continuous two-stage Cephalosporin C production

Cephalosporin is one of the most consumed antibiotics for its effectiveness against a wide variety of infections. Most cephalosporin products are the semi-derivatives of Cephalosporin C (CPC), a metabolite of the fungus Acremonium chrysogenum. Since naturally the desired metabolite is not produced in a large amount by the fungus, an innovative operational strategy is required to increase its yield for the production of the antibiotic to be economically feasible. One way to increase the cephalosporin productivity is by increasing the concentration of thin hyphae cell in the bioreactor, but this will lead to a higher blower power requirement for providing adequate availability of oxygen in the fermentation broth. Lack of oxygen will retard the growth rate and reduce the productivity. Conversely, excessive aeration of the fermentation broth will lead to high shear stress that can kill the cells. The present work investigates through dynamic simulation the effectiveness of a continuous two-stage aerobic fermentation for the CPC production. The operating conditions are optimized to determine an optimal trade-off between the cephalosporin productivity and blower power. An increase of the dissolved oxygen in the first bioreactor from 10 % to 20 % can increase CPC productivity by 75.5 % from 24.42 mg/L.hr to 42.86 mg/L.hr.

Activated Olive Stones as a Low-Cost and Environmentally Friendly Adsorbent for Removing Cephalosporin C from Aqueous Solutions

In this paper, we describe the removal of cephalosporin C (CPC) from aqueous solutions by adsorption onto activated olive stones (AOS) in a stirred tank. For comparative purposes, several experiments of adsorption onto commercial granular activated carbon were carried out. A quantum study of the different species of cephalosporin C that, depending on the pH, exist in aqueous solution pointed to a favorable mass transfer process during adsorption. Activated olive stones were characterized by SEM, EDX and IR techniques and their pHzc was determined. A 10−3 M HCl cephalosporin C solution has been selected for the adsorption experiments because at the pH of that solution both electrostatic and hydrogen bond interactions are expected to be established between the adsorbate and the adsorbent. The adsorption process is best described by the Freundlich isotherm model and the pseudo-second-order kinetic model, while the adsorption mechanism is mainly controlled by film diffusion. Under the conditions studied, the adsorption process is of a physical nature, endothermic and spontaneous. Comparison of the adsorption results obtained in this paper with those of other authors shows that the efficiency of AOS is 20% of that of activated carbon but 65% higher than that of the XAD-2 adsorbent. Considering its low price, abundance, easy accessibility and eco-compatibility, the use of activated olive stones as adsorbents for the removal of emerging pollutants from aqueous solutions represents an interesting possibility from both the economic and the environmental points of view.