29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp NBRC 110955
29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp NBRC 110955
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DOI：
10.1016/j.jbiosc.2015.04.004
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发表时间：
2015-12-01
影响因子：
2.8
通讯作者：
Nihira, Takuya
中科院分区：
文献类型：
--
作者：
Daduang, Ratama;Kitani, Shigeru;Nihira, Takuya
Maklamicin是一种由小单孢菌产生的螺三磷酸类抗生素。NBRC 110955，以及聚酮装配线和甘油酸酯利用系统参与其生物合成。生物合成的一个剪裁步骤被预测为后聚酮合成酶(PKS)修饰，这似乎是由假定的细胞色素P450单加氧酶MakC2和/或MakC3催化的。在这项研究中，我们对maklamicin生物合成过程中的makC2和makC3进行了表征，并从makC2干扰物中鉴定了一个新的maklamicin类似物。MakC2基因缺失导致maklamicin产量完全丧失，并伴随新化合物(29-deoxmaklamicin)的积累，而makC3基因缺失不影响maklamicin产量，表明29-deoxmaklamicin是maklamicin生物合成途径的中间产物，应作为makC2的底物。29-脱氧麦克拉米星对革兰氏阳性菌表现出较强或中等的抗微生物活性。异源表达makC2的阿维链霉菌成功地将29-脱氧maklamicin转化为maklamicin，证实了makC2是形成成熟maklamicin的最后一步羟基酶。(C)2015年，日本生物技术学会。版权所有。
Maklamicin is a spirotetronate-class antibiotic produced by Micromonospora sp. NBRC 110955, and a polyketide assembly line and a glycerate utilization system are involved in its biosynthesis. One tailoring step in the biosynthesis is predicted to be post-polyketide synthase (PKS) modification, which seems to be catalysed by putative cytochrome P450 monooxygenases, MakC2 and/or MakC3. In this study, we characterized makC2 and makC3 in the biosynthesis of maklamicin and identified a new maklamicin analogue from a makC2 disruptant. Gene deletion of makC2 resulted in the complete loss of maklamicin production with concomitant accumulation of a new compound (29-deoxymaklamicin), while gene deletion of makC3 did not affect the maklamicin production, indicating that 29-deoxymaklamicin is an intermediate in the biosynthetic pathway of maklamicin and should serve as the substrate of MakC2. 29-Deoxymaklamicin showed strong-to-modest anti-microbial activity against gram-positive bacteria. The fact that Streptomyces avermitilis heterologously expressing makC2 successfully converted 29-deoxymaklamicin into maklamicin confirmed that MakC2 is the final-step hydroxylase in the formation of mature maklamicin. (c) 2015, The Society for Biotechnology, Japan. All rights reserved.