Enhanced cephalosporin C production with a combinational ammonium sulfate and DO-Stat based soybean oil feeding strategy

A novel substrates feeding strategy by coupling ammonium sulfate addition with soybean oil feeding was proposed for efficient cephalosporin C (CPC) production by Acremonium chrysogenum and testified in a 7 L fermentor to maintain NH4+N concentration stably for normal mycelium differentiation. On the base of the coupling strategy, fermentation performance during main CPC production phase with different soybean oil feeding methods was compared. The results indicated that the modified DO-Stat soybean oil feeding strategy, namely, the method of adopting DO-Stat for soybean oil feeding and using O2-enriched air for aeration, could maintain CPC synthesis rate at an appropriately high level and reduce deacetoxycephalosporin (DAOC, the major by-product of CPC fermentation) accumulation simultaneously. The modified DO-Stat soybean oil feeding strategy could raise final CPC concentration up to a high level of 35.77 g/L and lower DAOC concentration down to a level of 0.178 g/L, so that the quality standard of CPC fermentation product could be satisfied by controlling DAOC/CPC ratio below 0.5%. The metabolic analysis revealed that a weakened carbon flux distribution in TCA was beneficial for reducing DOAC overflow.

► Final CPC concentration reached 35.77 g/L and DAOC stayed at 0.178 g/L, DAOC/CPC was below 0.5% ensuring CPC products quality.
► Overall operation cost in CPC fermentation was relieved.
► Metabolic analysis revealed that a weakened carbon flux distribution in TCA was beneficial for reducing DOAC overflow.