Lee Sang Kil, Basnet Devi B, Choi Cha Yong, Sohng Jae Kyung, Ahn Jong Seog, Yoon Yeo Joon
School of Chemical Engineering, College of Engineering, Seoul National University, San 56-1, Sinlim-dong, Gwanak-gu 151-742, Republic of Korea.
Bioorg Chem. 2004 Dec;32(6):549-59. doi: 10.1016/j.bioorg.2004.06.002.
The substrate flexibility of the erythromycin C-12 hydroxylase from Saccharopolyspora erythraea, EryK, was investigated to test its potential for the generation of novel polyketide structures. We have shown that EryK can accept the substrates of PikC from Streptomyces venezuelae which is responsible for the hydroxylation of YC-17 and narbomycin. In a S. venezuelae pikC deletion mutant, EryK could catalyze the hydroxylation of YC-17 and narbomycin to generate methymycin/neomethymycin and pikromycin, respectively. Molecular modeling of the enzyme-substrate complex suggested the possible interaction of EryK with alternative substrates. The results indicate that EryK is flexible toward some alternative polyketides and can be useful for structural diversification of macrolides by post-polyketide synthase hydroxylation.
对来自糖多孢红霉菌的红霉素C-12羟化酶EryK的底物灵活性进行了研究，以测试其生成新型聚酮化合物结构的潜力。我们已经表明，EryK可以接受委内瑞拉链霉菌中负责YC-17和纳博霉素羟基化的PikC的底物。在委内瑞拉链霉菌pikC缺失突变体中，EryK可以分别催化YC-17和纳博霉素的羟基化反应，生成美他霉素/新美他霉素和匹克罗霉素。酶-底物复合物的分子模拟表明EryK与替代底物可能存在相互作用。结果表明，EryK对一些替代聚酮化合物具有灵活性，并且可用于通过聚酮化合物合酶后羟基化实现大环内酯类化合物的结构多样化。
