Comparative metabolomic study of Penicillium chrysogenum during pilot and industrial penicillin fermentations

Comparative metabolomics was carried out to investigate the metabolic differences of Penicillium chrysogenum in the pilot and industrial fermentations that resulted from the scale-up. By principal component analysis, the early stages of two fermentation processes were clearly distinguished, whereas the middle and final stages were clustered together. It indicated that the different metabolisms of cells in the pilot and industrial fermentations mainly existed during the early stage. Furthermore, the levels of polyamines, polyols, glycolysis, and tricarboxylic acid cycle intermediates, which changed more dramatically during the pilot process, were all higher in the pilot than in the industrial fermentation during the early stage. This indicated that the fermentation conditions of the early stage should be the focus of process management which is aimed at increasing penicillin production. Additionally, the comparative accumulations of the precursors of penicillin (valine, cysteine, and lysine) revealed that penicillin biosynthesis in the industrial process was more affected during the middle stage of fermentation. These findings provide new insights to further regulate the industrial process and improve the production of penicillin. More generally, this study attempts to address the scarcity of studies that contrast the metabolic outcomes between commercial- and pilot-scale conditions.