The present invention discloses a method for producing novel lactam antibiotics by using specific engineered bacteria transformant BL21(DE3)/PET28-ASPGA. According to the method, a penicillin acylase amino acid sequence represented by SEQIDNO:1 is adopted as basis, a mutation site is introduced, reverse design is performed to obtain a nucleotide sequence, optimization is performed, complete gene synthesis and recombinant vector construction are sequentially performed to construct a recombinant strain, and the constructed recombinant strain is treated through steps of fermentation, cell disruption, separation, purification, decoloration and immobilization to finally obtain the novel lactam antibiotic immobilized enzyme finished product capable of being directly used for industrial production. According to the present invention, the immobilized enzyme prepared by using the method has characteristics of high enzyme activity, good stability and excellent repeated use effect, and can be provided for catalyzing synthesis of a variety of lactam antibiotics such as amoxicillin, cephalexin and cefaclor.