Synergistic actions of tailoring enzymes in pradimicin biosynthesis.
Synergistic actions of tailoring enzymes in pradimicin biosynthesis.
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DOI：
10.1002/cbic.201402306
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发表时间：
2014-10-13
期刊：
影响因子：
3.2
通讯作者：
Zhan, Jixun
中科院分区：
文献类型：
--
作者：
Napan, Kandy;Zhang, Shuwei;Morgan, Whitney;Anderson, Thomas;Takemoto, Jon Y.;Zhan, Jixun
研究了pradimicin生物合成中的三个关键裁剪酶PdmJ、PdmW和PdmN。通过对产物6-羟基- g - 2a的结构表征，确定PdmW为C-6羟化酶。当PdmJ和PdmW分别与形成G-2A的早期生物合成酶单独表达时，分别催化C-5和C-6羟基化的效率较低。当这两种细胞色素P450酶共表达时，有效地产生了二羟基化产物5,6-二羟基- g - 2a，表明这两种酶在pradimicin生物合成中协同作用。异源表达的PdmN在冷色链霉菌CH999中通过将d -丙氨酸连接到羧基上，将G-2A转化为JX137a。PdmN对氨基酸供体和受体的底物特异性较弱。通过组合生物合成，生产了一系列新的普拉迪米星类似物。
Three key tailoring enzymes PdmJ, PdmW and PdmN in pradimicin biosynthesis were investigated. PdmW was characterized as the C-6 hydroxylase by structural characterization of the corresponding product 6-hydroxy-G-2A. The efficiencies of the C-5 and C-6 hydroxylations catalyzed respectively by PdmJ and PdmW were low when they were expressed individually with the early biosynthetic enzymes that form G-2A. When these two cytochrome P450 enzymes were co-expressed, a dihydroxylated product 5,6-dihydroxy-G-2A was efficiently produced, indicating that these two enzymes work synergistically in pradimicin biosynthesis. Heterologously expressed PdmN in Streptomyces coelicolor CH999 converted G-2A to JX137a by ligating a unit of D-alanine to the carboxyl group. PdmN has relaxed substrate specificity toward both amino acid donors and acceptors. Through combinatorial biosynthesis, a series of new pradimicin analogues were produced.
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影响因子：
3.2
作者：
Zhan, Jixun;Qiao, Kangjian;Tang, Yi
通讯作者：
Tang, Yi
影响因子：
3.2
作者：
Zhan, Jixun;Watanabe, Kenji;Tang, Yi
通讯作者：
Tang, Yi
DOI：
10.1111/j.1749-6632.1988.tb40402.x
发表时间：
1988-01-01
影响因子：
5.2
作者：
Oki, T;Saitoh, K;Kawaguchi, H
通讯作者：
Kawaguchi, H
影响因子：
2.7
作者：
Napan, Kandy L.;Zeng, Jia;Takemoto, Jon Y.;Zhan, Jixun
通讯作者：
Zhan, Jixun
影响因子：
56.9
作者：
MCDANIEL, R;EBERTKHOSLA, S;KHOSLA, C
通讯作者：
KHOSLA, C