Decreased production of para-hydroxypenicillin V in penicillin V fermentations.
Penicillin V (phenoxymethyl penicillin) is produced by industrial strains of Penicillium chrysogenum in the presence of phenoxyacetic acid (POAc), a side-chain precursor for the penicillin V molecule. The wild-type strain of P. chrysogenum produces an undesirable penicillin byproduct, para-hydroxypenicillin V (p-OH penicillin V), in addition to penicillin V, via para-hydroxylation of POAc and subsequent incorporation of the p-OH phenoxyacetic acid into the penicillin molecule. Most of the p-OH penicillin V is produced late in cycle when the POAc concentration in the medium is nearly depleted. The level of p-OH penicillin V produced by the control strain ranges up to 10-15% of the total penicillins produced. 3-Phenoxypropionic acid and p-bromophenylacetic acid partially inhibit the formation of p-OH penicillin V with a minimal effect on penicillin V productivity. Mutants deficient in their ability to hydroxylate POAc were found to produce lower levels of p-OH penicillin V. Multi-step mutation and screening, starting with the wild-type strain, have culminated in isolation of mutants which produce p-OH penicillin V as 1% of the total penicillins with no adverse effect on penicillin V productivity.
Bristol-Myers Squibb Company, Industrial Division, Syracuse, NY 13221-4755.
L T
LT
Chang
E L
EL
McGrory
R P
RP
Elander
D J
DJ
Hook
D005285:Fermentation; D006900:Hydroxylation; D007700:Kinetics; D016296:Mutagenesis; D010404:Penicillin V / Q000031:analogs & derivatives* / Q000378:metabolism*; D010408:Penicillium chrysogenum / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D010642:Phenoxyacetates / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism; D014466:Ultraviolet Rays
D010642:Phenoxyacetates; D010648:Phenylacetates; C060825:4-hydroxypenicillin V; D010404:Penicillin V