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    • 3. 发明申请
    • IMPROVED IN VIVO PRODUCTION OF CEPHALOSPORINS
    • 改善头孢菌素的体内生产
    • WO0037671A3
    • 2000-09-14
    • PCT/EP9910292
    • 1999-12-21
    • DSM NVBOVENBERG ROELOF ARY LANSKERKMAN RICHARDKOENHEN ERIC
    • BOVENBERG ROELOF ARY LANSKERKMAN RICHARDKOENHEN ERIC
    • C12P35/06C12N9/10C12P35/00C12R1/82
    • C12P35/00C12N9/1029
    • The present invention discloses a process for the production of 7-amino cephalosporanic acid (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.
    • 本发明公开了生产7-氨基头孢菌酸(7-ACA)或其衍生物的方法,其包括发酵产黄青霉菌菌株的步骤,所述产黄青霉菌菌株用包含编码扩环酶,羟化酶和乙酰​​转移酶的核苷酸序列的表达构建体转化 在合适的酰基侧链前体或其盐或酯存在下的活性,从而产生N-酰化的7-ACA化合物,将由此产生的N-酰化的7-ACA化合物N-脱酰基化,和任选地酰化 游离氨基和/或用适于形成头孢菌素抗生素的侧链取代3'乙酸酯基团,其特征在于编码乙酰转移酶的核苷酸序列来自Acremonium chrysogenum并开始于开放阅读框的第二个ATG, 存在于所述核苷酸序列中。