Expression of cefF significantly decreased deacetoxycephalosporin C formation during cephalosporin C production in Acremonium chrysogenum.

Deacetoxycephalosporin C (DAOC) is not only the precursor but also one of the by-products during cephalosporin C (CPC) biosynthesis. One enzyme (DAOC/DAC synthase) is responsible for the two-step conversion of penicillin N into deacetylcephalosporin C (DAC) in Acremonium chrysogenum, while two enzymes (DAOC synthase and DAOC hydroxylase) were involved in this reaction in Streptomyces clavuligerus and Amycolatopsis lactamdurans (Nocardia lactamdurans). In this study, the DAOC hydroxylase gene cefF was cloned from Streptomyces clavuligerus and introduced into Acremonium chrysogenum through Agrobacterium tumefaciens-mediated transformation. When cefF was expressed under the promoter of pcbC, the ratio of DAOC/CPC in the fermentation broth significantly decreased. These results suggested that introduction of cefF could function quite well in Acremonium chrysogenum and successfully reduce the content of DAOC in the CPC fermentation broth. This work offered a practical way to improve the CPC purification and reduce its production cost.