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The specific mGST activity unlike the cytosolic GST (cGST) activity increased substantially when the penicillin side\u2010chain precursor phenoxyacetic acid (POA) was included in the culture medium. Therefore, a microsomal monooxygenase (causing possible release of epoxide intermediates) and mGST\u2010dependent detoxification pathway may exist for the side\u2010chain precursors as an alternative to microsomal activation to acyl\u2010CoA and subsequent transfer to \u03b2\u2010lactam molecules. The <jats:italic>P. chrysogenum pahA<\/jats:italic> and <jats:italic>Aspergillus nidulans phacA<\/jats:italic> gene products, which are cytochrome P450 monooxygenases and are able to hydroxylate phenylacetic acid (PA) at position 2 on the aromatic ring, are unlikely to release toxic epoxide intermediates but epoxidation of PA and POA due to the action of other microsomal monooxygenases cannot be excluded. The GSH\u2010dependent detoxification of POA was provoked by a well\u2010controlled transient lowering of pH (down to 5.0) at the beginning of the production phase in a fed\u2010batch fermentation system. Both the specific GST and \u03b3GT activities were increased but the intracellular GSH concentrations remained unaltered unless the pH of the feed was transiently lowered below 5.0. At pH 4.6, the GSH pool was depleted rapidly but no antibiotic production was observed. Although sucrose was taken up effectively by the cells, cell death and autolysis were progressing. Therefore, the industrial exploitation of the GSH\u2010dependent detoxification of penicillin side\u2010chain precursors to reduce intracellular GSH\u2010levels in order to avoid the GSH inhibition of the \u03b2\u2010lactam biosynthetic enzymes seems to be rather unlikely. <jats:italic>P. chrysogenum<\/jats:italic> mGST and cGST were separated using GSH\u2010Sepharose 6B affinity chromatography. The purified cGST possessed a homodimer (<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>) tertiary structure with <jats:italic>M<jats:sub>r<\/jats:sub><\/jats:italic><jats:sub>, <jats:italic>\u03b1<\/jats:italic><\/jats:sub> = 29500.<\/jats:p>","DOI":"10.1002\/jobm.200390032","type":"journal-article","created":{"date-parts":[[2003,7,15]],"date-time":"2003-07-15T15:08:35Z","timestamp":1058281715000},"page":"287-300","source":"Crossref","is-referenced-by-count":7,"title":["Does the detoxification of penicillin side\u2010chain precursors depend on microsomal monooxygenase and glutathione S\u2010transferase in <i>Penicillium chrysogenum<\/i>?"],"prefix":"10.1002","volume":"43","author":[{"given":"Tam\u00e1s","family":"Emri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitta","family":"Ol\u00e1h","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"S\u00e1mi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"P\u00f3csi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,7,15]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(85)13073-9"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1042\/bj0960595","article-title":"The gel\u2010filtration behaviour of proteins related to their molecular weights over a wide range","volume":"96","author":"Andrews P.","year":"1965","journal-title":"Biochem. 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