PURPOSE: To obtain the subject compd. in high yield which is useful as an antibiotic by enzymatically condensing a reaction deriv. of an α-substd.-α-aminoacid and a cephalosphorin matrix.

CONSTITUTION: A compd. expressed by formula I (R is a hydrocarbon ring or a heteroring; the hydroxy group in the carboxy may be substd. with an org. group) is reacted with a compd. expressed by formula II (R1 is H, a halogen, methoxy or the like; R2 is H or a carboxy protecting group) in the presence of an immobilized penicillin acylase enzyme in a solvent (e.g. water) at 0 to 20°C to obtain a cephalosporin expressed by formula III. The reaction is carried out under the conditions described below independently or in combination: (1) The reaction temp. is controlled to 0 to 20°C. (2) The pH of the reaction liquid is not controlled but changes in pH are allowed to stand. (3) The α-amino acid is used in a high molar ratio to the cephalosporanic nucleus.