Microbial transformation of aniline to acetaminophen |
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Authors: | Sang Sup Lee Hyung Jong Jin Mi Won Son |
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Institution: | 1. College of Pharmacy, Seoul National University, Seoul, Korea
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Abstract: | In order to obtain acetaminophen, a popular analgesic-antipyretic, through microbial p-hydroxylation and N-acetylation of
aniline, various fungi and bacteria were screened. Among them,Streptomyces species were chosen for strain improvement by the use of interspecific protoplast fusion technique. Two interspecific fused
strains were developed betweenS. rimosus (N-cetylation function) andS. aureofaciens (p-hydroxylation function) and also betweenS. lividans andS. globisporus. For efficient protoplast fusion and cell wall regeneration, various conditions were examined. In a typical experiment of
mixedS. rimosus (pro− his−) andS. aureofaciens (ilv−) protoplasts with 40% (w/v) polyethylene glycol 3350 (PEG) for 3 min gave 8.3×10−7 of fusion frequency. Treatment of mixedS. lividans (pant−) andS. globisporus (leu−) protoplasts with 50% (w/v) PEG for 3 min at 30°C gave 1.2×10−6 of frequency. Among the fused strains, up to 40–50% increase in p-hydroxylation power was observed. To investigate the possibility
of plasmid involvement in p-hydroxylation of acetanilide, plasmid curing was attempted. We found that cells treated with acriflavine
(at the frequency of 100%) and cells regenerated from protoplsts ofS. aureofaciens (2% frequency) lost their p-hydroxylation function. |
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Keywords: | Protoplast fusion plasmid curing p-hydroxylation of aniline |
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