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

Ogasawara, Yasushi; Nakagawa, Yo; Maruyama, Chitose; Hamano, Yoshimitsu; Dairi, Tohru

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

Ogasawara, Yasushi; Nakagawa, Yo; Maruyama, Chitose et al.

Bioorganic & medicinal chemistry letters, 2019, 29(16), 2076-2078

Permalink : https://hdl.handle.net/2115/82450

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アクセス権	open access
URI	https://hdl.handle.net/2115/82450
タイトル	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
著者	Ogasawara, Yasushi ; Nakagawa, Yo ; Maruyama, Chitose ; Hamano, Yoshimitsu ; Dairi, Tohru
e-Rad_Researcher 20732986 著者名 Ogasawara, Yasushi
著者名 Nakagawa, Yo
著者名 Maruyama, Chitose
著者名 Hamano, Yoshimitsu
著者名 Dairi, Tohru
言語	英語
キーワード	Acyl carrier protein
	Antibiotics
	Biosynthesis
	Glycosyltransferase
	Mitomycin
発行日	2019-08-15
出版者	Elsevier
収録物名	Bioorganic & medicinal chemistry letters
巻(号)	29(16)
ページ	2076-2078
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0960-894X
NCID	AA1079577X
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.bmcl.2019.07.009