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.
Department of Microbiology, University of Alberta, Edmonton, Canada.
M J
MJ
Rollins
S E
SE
Jensen
S
S
Wolfe
D W
DW
Westlake
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