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Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics
| Title: | Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics |
| Authors: | Hirose, Yuki Browse this author | | Watanabe, Kenji Browse this author | | Minami, Atsushi Browse this author | | Nakamura, Takemichi Browse this author | | Oguri, Hiroki Browse this author | | Oikawa, Hideaki Browse this author |
| Keywords: | biosynthesis | | echinomycin | | Streptomyces lasaliensis | | Streptomyces Sp | | SW-163D |
| Issue Date: | Jan-2011 |
| Publisher: | Japan Antibiotics Research Association |
| Journal Title: | Journal of Antibiotics |
| Volume: | 64 |
| Issue: | 1 |
| Start Page: | 117 |
| End Page: | 122 |
| Publisher DOI: | 10.1038/ja.2010.142 |
| PMID: | 21102595 |
| Abstract: | Quinomycin antibiotics, represented by echinomycin, are an important class of antitumor antibiotics. We have recently succeeded in identification of biosynthetic gene clusters of echinomycin and SW-163D, and have achieved heterologous production of echinomycin in Escherichia coil. In addition, we have engineered echinomycin nonribosomal peptide synthetase (NRPS) to generate echinomycin derivatives. However, the biosynthetic pathways of intercalative chromophores quinoxaline-2-carboxylic acid (QXC) and 3-hydroxyquinaldic acid (HQA), which are important for biological activity, were not fully elucidated. Here, we report experiments involving incorporation of a putative advanced precursor, (2S, 3R)-[6'-2H]-3-hydroxy-L-kynurenine, and functional analysis of the enzymes Swb1 and Swb2 responsible for late-stage biosynthesis of HQA. Based on these experimental results, we propose biosynthetic pathways for both QXC and HQA via the common intermediate 3-hydroxy-L-kynurenine. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/46763 |
| Appears in Collections: | 理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 及川 英秋
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