Comparative analysis of intracellular metabolites of Cephalosporium acremonium in pilot and industrial fermentation processes

To get a better understanding of the characteristics of Cephalosporium acremonium with higher productivity, C. acremonium cells in pilot and industrial fermentation processes were analyzed using the profiles of metabolites. The different metabolic features of cells in pilot and industrial processes were caused by the different fermentation environments. The hierarchical cluster analysis of the data of metabolic profiling revealed that the concentrations of most of the metabolites were higher in the industrial process than in the pilot one, especially at the cephalosporin C accumulation stage. The analysis of important metabolites of primary metabolism indicated that the ability of the cephalosporin C biosynthesis was higher in the industrial process than that in the pilot one in C. acremonium. The analysis of the variations of cephalosporin C precursors and amino acids that were related to these precursors suggested that the metabolic flux changes of a-aminoadipic acid and cysteine between the primary metabolism and cephalosporin biosynthetic pathway in the industrial process. Furthermore, metabolites of C. acremonium, such as proline, spermine, inositol phosphate, and glycerol, were shown to respond to the fermentation environmental stress. These findings provide insights into the intracellular metabolite characteristics and feasible regulation scheme to improve the titer of cephalosporin C in the industrial process.