Enhanced cephalosporin C production with a novel DO ‐Stat based carbon resources co‐feeding strategy

Background To solve the problems of high by‐product accumulations and low substrate utilization efficiencies in the traditional cephalosporin C ( CPC ) fermentation process, a novel DO ‐Stat based substrates co‐feeding strategy for CPC production by Acremonium chrysogenum ( A. chrysogenum ) was conducted in a 7 L fermentor using the addition of glucose coupled with soybean oil . RESULTS Compared with the sole soybean oil feeding method, the final CPC concentration was enhanced from 25.3 g L ‐1 to a higher level of 31.9 g L ‐1 by the novel substrate co‐feeding strategy. The major by‐product of deacetoxycephalosporin C ( DAOC ) was reduced from 0.32 g L ‐1 to a lower level of 0.092 g L ‐1 , and the final DAOC / CPC ratio (0.28%) reached the CPC fermentation quality standard (below 0.5%). Metabolic flux analysis revealed that the carbon fluxes in the CPC synthesis related route were increased about 2.2‐fold by applying the novel substrate co‐feeding strategy . Conclusion The results indicated that the co‐feeding of glucose and soybean oil in the main CPC production phase was desirable for CPC fermentation, and led to higher CPC production/yield and substrate utilization efficiencies but less DAOC accumulation. © 2013 Society of Chemical Industry