Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics

• Hirose, Yuki

• Watanabe, Kenji

• Minami, Atsushi

• Nakamura, Takemichi

• Oguri, Hiroki

• Oikawa, Hideaki

抄録

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.

収録刊行物

• Journal of Antibiotics

  Journal of Antibiotics 64 (1), 117-122, 2011-01

  Japan Antibiotics Research Association

キーワード

• biosynthesis
• echinomycin
• Streptomyces lasaliensis
• Streptomyces Sp
• SW-163D

詳細情報

• CRID: 1050564288960649344
• NII論文ID: 10030637815
• NII書誌ID: AA0069330X
• HANDLE: 2115/46763
• ISSN: 00218820
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles