Oxygen derepresses deacetoxycephalosporin C synthase and increases the conversion of penicillin N to cephamycin C in Streptomyces clavuligerus.
When dissolved oxygen (DO) was maintained at saturation level during batch fermentations of Streptomyces clavuligerus (NRRL 3585), the accumulation of the intermediate penicillin N was lowered while formation of the end product cephamycin C was increased relative to fermentations without DO control. The specific activity of the penicillin ring-expansion enzyme deacetoxycephalosporin C synthase (DAOCS) was increased 2.3-fold under oxygen saturated conditions, whereas the penicillin ring-cyclizing enzyme isopenicillin N synthase (IPNS) showed only a 1.3-fold increase. Thus oxygen derepression of DAOCS appears to be an important regulatory mechanism in the conversion of penicillin N to cephamycin C in S. clavuligerus. IPNS, an early acting enzyme in cephamycin C biosynthesis, and DAOCS, which acts late in the pathway, both disappeared from cell extracts at 60 h, just prior to cessation of cephamycin production.
Rollins
M J
MJ
Department of Microbiology, University of Alberta, Edmonton, Canada.
Jensen
S E
SE
Wolfe
S
S
Westlake
D W
DW
D002513:Cephamycins / Q000096:biosynthesis*; D005285:Fermentation; D019751:Intramolecular Transferases; D007535:Isomerases / Q000096:biosynthesis*; D007700:Kinetics; D010088:Oxidoreductases / Q000096:biosynthesis; D010100:Oxygen / Q000494:pharmacology*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism*; D013302:Streptomyces / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D002513:Cephamycins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010088:Oxidoreductases; C038370:isopenicillin N synthetase; D007535:Isomerases; D019751:Intramolecular Transferases; C038371:deacetoxycephalosporin C synthetase; C006414:penicillin N; D010100:Oxygen; C024925:cephamycin C