Determination of the rate-limiting step(s) in the biosynthetic pathways leading to penicillin and cephalosporin.

This paper is a review of strategies that have been used, or that could be used, to determine the rate-limiting step(s) in the biosynthetic pathways leading to penicillin or cephalosporin. Information is summarized from published material that involves studies with low-producing strains of Penicillium chrysogenum and Cephalosporium acremonium. We also summarize information derived from some high-producing production strains. Identification of the rate-limiting step(s) was of great interest to us as the first step in a rational program to further improve antibiotic titers of these highly developed strains. A number of approaches that could be used to elucidate the rate-limiting step(s) are described herein.