Chang L T, McGrory E L, Elander R P, Hook D J
Bristol-Myers Squibb Company, Industrial Division, Syracuse, NY 13221-4755.
J Ind Microbiol. 1991 Apr;7(3):175-9. doi: 10.1007/BF01575880.
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.
青霉素V（苯氧甲基青霉素）由产黄青霉的工业菌株在苯氧乙酸（POAc）存在的情况下产生，苯氧乙酸是青霉素V分子的侧链前体。产黄青霉的野生型菌株除了产生青霉素V外，还会通过POAc的对羟基化以及随后将对羟基苯氧乙酸掺入青霉素分子中，产生一种不良的青霉素副产物，对羟基青霉素V（p-OH青霉素V）。大多数对羟基青霉素V是在培养基中POAc浓度几乎耗尽的培养周期后期产生的。对照菌株产生的对羟基青霉素V水平高达所产生的总青霉素的10%-15%。3-苯氧基丙酸和对溴苯乙酸部分抑制对羟基青霉素V的形成，而对青霉素V的生产力影响最小。发现缺乏将POAc羟基化能力的突变体产生的对羟基青霉素V水平较低。从野生型菌株开始的多步突变和筛选最终分离出了突变体，这些突变体产生的对羟基青霉素V占总青霉素的1%，且对青霉素V的生产力没有不利影响。
