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Constructing multi-enzymatic cascade reactions for selective production of 6-bromoindirubin from tryptophan in Escherichia coli
DC Field | Value | Language |
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dc.contributor.author | Lee, Jeongchan | - |
dc.contributor.author | Kim, Joonwon | - |
dc.contributor.author | Kim, Hyun | - |
dc.contributor.author | Park, Hyun A. | - |
dc.contributor.author | Kim, Jin Young | - |
dc.contributor.author | Kim, Eun-Jung | - |
dc.contributor.author | Yang, Yung-Hun | - |
dc.contributor.author | Choi, Kwon-Young | - |
dc.contributor.author | Kim, Byung-Gee | - |
dc.date.accessioned | 2022-10-07T01:27:34Z | - |
dc.date.available | 2022-10-07T01:27:34Z | - |
dc.date.created | 2022-09-20 | - |
dc.date.issued | 2022-10 | - |
dc.identifier.citation | Biotechnology and Bioengineering, Vol.119 No.10, pp.2938-2949 | - |
dc.identifier.issn | 0006-3592 | - |
dc.identifier.uri | https://hdl.handle.net/10371/185577 | - |
dc.description.abstract | 6-Bromoindirubin (6BrIR), found in Murex sea snails, is a precursor of indirubin-derivatives anticancer drugs. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and difficulties in site-specific bromination and oxidation at the indole ring. Here, we present an efficient 6BrIR production strategy in Escherichia coli by using four enzymes, that is, tryptophan 6-halogenase fused with flavin reductase Fre (Fre-L3-SttH), tryptophanase (TnaA), toluene 4-monooxygenase (PmT4MO), and flavin-containing monooxygenase (MaFMO). Although most indole oxygenases preferentially oxygenate the electronically active C3 position of indole, PmT4MO was newly characterized to perform C2 oxygenation of 6-bromoindole with 45% yield to produce 6-bromo-2-oxindole. In addition, 6BrIR was selectively generated without indigo and indirubin byproducts by controlling the reducing power of cysteine and oxygen supply during the MaFMO reaction. These approaches led to 34.1 mg/L 6BrIR productions, making it possible to produce the critical precursor of the anticancer drugs only from natural ingredients such as tryptophan, NaBr, and oxygen. | - |
dc.language | 영어 | - |
dc.publisher | Wiley - V C H Verlag GmbbH & Co. | - |
dc.title | Constructing multi-enzymatic cascade reactions for selective production of 6-bromoindirubin from tryptophan in Escherichia coli | - |
dc.type | Article | - |
dc.identifier.doi | 10.1002/bit.28188 | - |
dc.citation.journaltitle | Biotechnology and Bioengineering | - |
dc.identifier.wosid | 000850543800026 | - |
dc.identifier.scopusid | 2-s2.0-85135502433 | - |
dc.citation.endpage | 2949 | - |
dc.citation.number | 10 | - |
dc.citation.startpage | 2938 | - |
dc.citation.volume | 119 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kim, Byung-Gee | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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