IMPROVED IN VIVO PRODUCTION OF CEPHALOSPORINS

摘要

The present invention discloses a process for the production of 7-ACA or a derivative thereof comprising the steps of fermenting a P. chrysogenum strain being transformed with an expression construct comprising a nucleotide sequence encoding expandase, hydroxylase and acetyltransferase activity in the presence of a suitable acyl side chain precursor, or a salt or ester thereof, such that an N-acylated 7-ACA compound is produced, N-deacylating the thus produced N-acylated 7-ACA compound and, optionally, acylating the free amino group and/or substituting the 3' acetate group with a side chain suitable to form a cephalosporin antibiotic, characterised in that the nucleotide sequence encoding the acetyltransferase is derived from Acremonium chrysogenum and starts at the second ATG of the open reading frame as present in said nucleotide sequence.