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.
Usher
J J
JJ
Bristol-Myers Squibb Company, Industrial Division, Syracuse, NY 13221-4755.
Hughes
D W
DW
Lewis
M A
MA
Chiang
S J
SJ
D000164:Acremonium / Q000378:metabolism; D002511:Cephalosporins / Q000096:biosynthesis*; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005285:Fermentation; D005818:Genetic Engineering; D007700:Kinetics; D010406:Penicillins / Q000096:biosynthesis*; D010408:Penicillium chrysogenum / Q000378:metabolism
D002511:Cephalosporins; D004798:Enzymes; D010406:Penicillins