Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens
Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens
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DOI：
10.1128/aac.01545-05
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发表时间：
2006-06-01
影响因子：
4.9
通讯作者：
Hucul, John A.
中科院分区：
文献类型：
--
作者：
Magarvey, Nathan A.;Haltli, Brad;Hucul, John A.
甘露肽霉素类抗生素是一类新型的脂糖肽类抗生素，具有抗多药耐药病原体的活性，具有潜在的临床有用的抗菌药物。这份报告是第一次描述这类新的甘露糖基化脂糖肽的生物合成。包括从吸水链霉菌NRRL 30439的甘露肽霉素生物合成基因簇的克隆、测序、注释和操作。甘露肽霉素生物合成基因簇内的基因编码的酶负责生成六肽核心（非核糖体肽合成酶[NRPS]）和剪裁反应（甘露糖基化、异戊酰化、羟基化和甲基化）。NRPS系统是非规范的，因为它具有六个模块，仅利用五个氨基酸特异性腺苷酸化结构域，并且它缺乏原型NRPS大环化硫酯酶结构域。对甘露肽霉素基因簇及其工程改造的分析阐明了甘露肽霉素的生物合成途径，并为生物合成新的和改进的甘露肽霉素提供了框架。
The mannopeptimycins are a novel class of lipoglycopeptide antibiotics active against multidrug-resistant pathogens with potential as clinically useful antibacterials. This report is the first to describe the biosynthesis of this novel class of mannosylated lipoglycopeptides. Included here are the cloning, sequencing, annotation, and manipulation of the mannopeptimycin biosynthetic gene cluster from Streptomyces hygroscopicus NRRL 30439. Encoded by genes within the mannopeptimycin biosynthetic gene cluster are enzymes responsible for the generation of the hexapeptide core (nonribosomal peptide synthetases [NRPS]) and tailoring reactions (mannosylation, isovalerylation, hydroxylation, and methylation). The NRPS system is noncanonical in that it has six modules utilizing only five amino acid-specific adenylation domains and it lacks a prototypical NRPS macrocyclizing thioesterase domain. Analysis of the mannopeptimycin gene cluster and its engineering has elucidated the mannopeptimycin biosynthetic pathway and provides the framework to make new and improved mannopeptimycins biosynthetically.