Comparison of the secondary metabolites in two scales of cephalosporin C (CPC) fermentation and two different post-treatment processes.
Cephalosporin C (CPC) is the precursor of a class of antibiotics that were more effective than traditional penicillins. CPC production is performed mainly through fermentation by Acremonium chrysogenum, whose secondary metabolism was sensitive to the environmental changes. In the present work, secondary metabolites were measured by ion-pair reversed-phase liquid chromatography tandemed with hybrid quadrupole time-of-flight mass spectrometry, and the disparity of them from two scales of CPC fermentations (pilot and industrial) and also two different post-treatment processes (oxalic acid and formaldehyde added and control) were investigated. When fermentation size was enlarged from pilot scale (50 l) to industrial scale (156,000 l), the remarkable disparities of concentrations and changing trends of the secondary metabolites in A. chrysogenum were observed, which indicated that the productivity of CPC biosynthesis was higher in the large scale of fermentation. Three environmental factors were measured, and the potential reasons that might cause the differences were analyzed. In the post-treatment process after industrial fermentation, the changes of these secondary metabolites in the tank where oxalic acid and formaldehyde were added were much less than the control tank where none was added. This indicated that the quality of the final product was more stable after the oxalic acid and formaldehyde were added in the post-treatment process. These findings provided new insight into industrial CPC production.
Key Laboratory of Systems Bioengineering, Ministry of Education and Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
Ying-Xiu
YX
Cao
Hua
H
Lu
Bin
B
Qiao
Yao
Y
Chen
Ying-Jin
YJ
Yuan
D015074:2-Aminoadipic Acid / Q000378:metabolism; D000164:Acremonium / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002511:Cephalosporins / Q000096:biosynthesis* / Q000378:metabolism; D005285:Fermentation; D009842:Oligopeptides / Q000378:metabolism; D010406:Penicillins / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D009842:Oligopeptides; D010406:Penicillins; C121743:bis(aminoadipyl)-cysteinyl-valine; C025071:deacetylcephalosporin C; D015074:2-Aminoadipic Acid; C025163:cephalosporin C; C006414:penicillin N