期刊
JOURNAL OF ANTIBIOTICS
卷 64, 期 1, 页码 117-122出版社
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2010.142
关键词
biosynthesis; echinomycin; Streptomyces lasaliensis; Streptomyces Sp; SW-163D
资金
- JSPS [20310126]
- MEXT [22108002]
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 coli. In addition, we have engineered echinomycin non-ribosomal peptide synthetase 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'-H-2]-3-hydroxy-L-kynurenine, and functional analysis of the enzymes Swb1 and Swb2 responsible for late-stage biosynthesis of HQA. On the basis of these experimental results, we propose biosynthetic pathways for both QXC and HQA through the common intermediate 3-hydroxy-L-kynurenine. The Journal of Antibiotics (2011) 64, 117-122; doi:10.10381ja.2010.142; published online 24 November 2010
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