Progress in combinatorial biosynthesis for drug discovery.
Progress in combinatorial biosynthesis for drug discovery.
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DOI：
10.1016/j.ddtec.2006.09.014
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Shen, Ben
中科院分区：
文献类型：
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作者：
Van Lanen, Steven G;Shen, Ben
组合生物合成是对天然产物生物合成机制进行遗传操作以获得结构多样性的过程，取决于几个因素，这里讨论的是两个关键因素：遗传信息的获取和酶的生化特性。前者的例子包括使用不寻常的化学实体，如氨基羟基苯甲酸起始单元，甲氧基丙二酸酯扩展单元，烯二炔核心和细菌芳香族聚酮化合物的生物合成的预测。后一方面包括模块化聚酮酶和非核糖体肽水解酶的结构域功能的继续阐明和新的生物化学途径，如环丙基单元和β-羟基酸的生物合成。最后，讨论了达托霉素和吲哚咔唑化合物的成功组合生物合成的实例。
Combinatorial biosynthesis, the process of genetic manipulations of natural product biosynthetic machinery for structural diversity, depends on several factors, and discussed here are two critical factors: access to genetic information and biochemical characterization of enzymes. Examples of the former include using predictions for the biosynthesis of unusual chemical entities such as aminohydroxybenzoic acid starter units, methoxymalonylate extender units, the enediyne core and bacterial aromatic polyketides. The latter aspect includes the continued elucidation of domain functionalities of modular polyketide synthases and nonribosomal peptide synthases and novel biochemical pathways such as the biosynthesis of a cyclopropyl unit and a beta-hydroxyl acid. Finally, examples of successful combinatorial biosynthesis for daptomycin and indolocarbozole compounds are discussed.: