Abstract:
PURPOSE OF WORK:Thymidine is an important precursor in antiviral drugs. We have enhanced thymidine production in E. coli by eliminating the repressors in the transcription of the gene coding for carbamoyl phosphate synthetase. The operon for carbamoyl phosphate synthetase (CarAB) in the thymidine biosynthesis regulatory pathway was derepressed by disrupting three known repressors (purR, pepA and argR). Combinatorial disruption of three repressors increased CarA expression levels in accordance with degree of disruption, which had a positive correlation with thymidine production. By simultaneous disruption of three repressors (BLdtugRPA), CarA expression level was increased by 3-fold compared to the parental strain, leading to an increased thymidine yield from 0.25 to 1.1 g thymidine l(-1). From BLdtugRPA, we established BLdtugRPA24 by transforming two plasmids expressing enzymes in the thymidine biosynthetic pathway and obtained 5.2 g thymidine l(-1) by Ph-stat fed-batch fermentation.
journal_name
Biotechnol Lettjournal_title
Biotechnology lettersauthors
Koo BS,Hyun HH,Kim SY,Kim CH,Lee HCdoi
10.1007/s10529-010-0413-7subject
Has Abstractpub_date
2011-01-01 00:00:00pages
71-8issue
1eissn
0141-5492issn
1573-6776journal_volume
33pub_type
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