Characterization of the biosynthetic gene cluster for maklamicin, a spirotetronate-class antibiotic of the endophytic Micromonospora sp. NBRC 110955.
Characterization of the biosynthetic gene cluster for maklamicin, a spirotetronate-class antibiotic of the endophytic Micromonospora sp. NBRC 110955.
复制标题
马卡霉素（一种内生小单孢菌属的螺环酯类抗生素）生物合成基因簇的表征。
DOI：
10.1016/j.micres.2015.07.003
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发表时间：
2015
期刊：
影响因子：
6.7
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
4)Daduang;R.;Kitani;S.;Hashimoto;J.;Thamchaipenet;A.;Igarashi;Y.;Ikeda;H. and Nihira;T.
Maklamicin，由内生小单孢菌产生。NBRC 110955是一种螺替膦酸类抗生素，具有抗革兰氏阳性菌的抗微生物活性，具有不同于其他螺替膦酸类抗生素的几个独特结构特征。在这里，我们描述了通过基因组测序草图，基因组文库筛选和基因破坏的mak生物合成（mak）基因簇的鉴定和表征。序列分析表明，一个合理的maklamicin簇存在于一个152 kb的DNA区域，编码46个开放阅读框，其中24个可以被分配在聚酮骨架，螺替乙二酸或周边部分的生物合成，自我抗性和maklamicin生产的调节作用。破坏聚酮合酶（PKS）基因makA1或makA4导致maklamicin生产的完全丧失，表明I型模块PKS系统负责maklamicin的生物合成。该基因簇包含一组用于形成tetronate部分的生物合成基因，发现其在螺tetronate抗生素的基因簇中高度保守。基于估算的生物合成基因，我们提出了maklamicin的生物合成途径。我们的研究结果不仅提供了对maklamicin中独特结构的生物合成机制的见解，而且还提供了有用的信息，以促进螺替膦酸酯生物合成途径的比较分析，以扩大结构库。
Maklamicin, which is produced by the endophyticMicromonosporasp. NBRC 110955, is a spirotetronate-class antibiotic possessing anti-microbial activity against Gram-positive bacteria, and has several unique structural features different from other spirotetronates. Here we describe identification and characterization of the maklamicin biosynthetic (mak) gene cluster through draft genome sequencing, genomic library screening, and gene disruption. Sequence analysis revealed that a plausible maklamicin cluster resides in a 152 kb DNA region encoding 46 open reading frames, 24 of which can be assigned roles in the biosynthesis of polyketide backbone, spirotetronate or peripheral moieties, self-resistance and the regulation of maklamicin production. Disruption of the polyketide synthase (PKS) genesmakA1ormakA4resulted in a complete loss of maklamicin production, indicating that the type I modular PKS system is responsible for the biosynthesis of maklamicin. Themakgene cluster contained a set of biosynthetic genes for the formation of a tetronate moiety, which were found to be highly conserved in the gene clusters for spirotetronate antibiotics. Based on the estimated biosynthetic genes, we propose the biosynthetic pathway for maklamicin. Our findings provide not only insights on the biosynthetic mechanism of the unique structures in maklamicin, but also useful information to facilitate a comparative analysis of the spirotetronate biosynthetic pathways to expand the structural repertoire.