Microbial Production of 7-Aminocepahlosporanic Acid and New Generation Cephalosporins (Cephalothin) by Different Processing Strategies

Abstract

The development of β-lactam antibiotics has been a continious battle of the design of new compounds to withstand inactivation by the ever-increasing diversity of β-lactamases. Semisynthetic cephalosporins like cephalothin were synthesized from 7-Amino cephalosporanic acid (7-ACA), and thiophene-2-actetic acid using cephalosporin-C acylase enzyme was studied. The production of cephalosporin-C acylase by Pseudomonas diminuta was used and the growth kinetics studied. The optimum condition of enzyme activity was determined by using response surface methodology. A 2³ full-factorial composite design was employed for experimental design and the result analyzed. The pH value and temperature for optimum activity were 6.5 and 32°C, respectively. The structural analog compound similar to the side-chain of semisynthetic cephalosporins, e.g., thiophene-2-actetic acid, was added. HPLC data analysis indicate that the concentration of cephalothin was 1.6 mg/mL.

Keywords:

• Central composite design
• Cephalothin
• Cephalosporin acylase
• Response surface methodology