In vitro characterization of MitE and MitB: Formation of N-acetylglucosaminyl-3-amino-5-hydroxybenzoyl-MmcB as a key intermediate in the biosynthesis of antitumor antibiotic mitomycins
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Abstract
Mitomycins, produced by several Streptomyces strains, are potent anticancer antibiotics that comprise an aziridine ring fused to a tricyclic mitosane core. Mitomycins have remarkable ability to crosslink DNA with high efficiency. Despite long clinical history of mitomycin C, the biosynthesis of mitomycins, especially mitosane core formation, remains unknown. Here, we report in vitro characterization of three proteins, MmcB (acyl carrier protein), MitE (acyl AMP ligase), and MitB (glycosyltransferase) involved in mitosane core formation. We show that 3-amino-5-hydroxybenzoic acid (AHBA) is first loaded onto MmcB by MitE at the expense of ATP. MitB then catalyzes glycosylation of AHBA-MmcB with uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) to generate a key intermediate, GlcNAc-AHBA-MmcB, which contains all carbon and nitrogen atoms of the mitosane core. These results provide important insight into mitomycin biosynthesis.
Journal
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- Bioorganic & medicinal chemistry letters
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Bioorganic & medicinal chemistry letters 29 (16), 2076-2078, 2019-08-15
Elsevier
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Details 詳細情報について
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- CRID
- 1050852095356624384
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- NII Article ID
- 120007132051
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- NII Book ID
- AA1079577X
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- HANDLE
- 2115/82450
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- ISSN
- 0960894X
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN