Coordinated and Iterative Enzyme Catalysis in Fungal Polyketide Biosynthesis.
Coordinated and Iterative Enzyme Catalysis in Fungal Polyketide Biosynthesis.
复制标题
DOI：
10.1021/acscatal.6b01559
复制
发表时间：
2016-09-02
期刊：
影响因子：
12.9
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Hang L;Liu N;Tang Y
真菌聚酮化合物是具有丰富化学多样性的天然产物，具有广泛的生物活性。这种化学多样性源于负责天然产物生物合成的生物合成基因簇中编码的专门酶。真菌聚酮合酶（PKS）是产生分子碳支架的巨合酶。随后的下游定制酶（例如加氧酶）将进一步修饰有机框架。在真菌中，许多酶被发现可以反复发挥作用——催化底物不同位点上的多个反应。该视角将分析由支架构建迭代 PKS 和伴随的迭代剪裁加氧酶组装而成的真菌聚酮化合物的几个示例。在这些示例中，PKS 产品专为下游迭代充氧而设计，以产生额外的复杂性。这些迭代酶共同协调精细天然产物的高效生物合成，例如洛伐他汀、毛球蛋白 A、细胞松弛素 E 和金华汀 E。
Fungal polyketides are natural products with great chemical diversity that exhibit a wide range of biological activity. This chemical diversity stems from specialized enzymes encoded in the biosynthetic gene cluster responsible for the natural product biosynthesis. Fungal polyketide synthases (PKS) are the megasynthases that produce the carbon scaffolds for the molecules. Subsequent downstream tailoring enzymes such as oxygenases will then further modify the organic framework. In fungi, many of these enzymes have been found to work iteratively—catalyzing multiple reactions on different sites of the substrate. This perspective will analyze several examples of fungal polyketides that are assembled from a scaffold-building iterative PKS and an accompanying iterative tailoring oxygenase. In these examples, the PKS product is designed for downstream iterative oxygenations to generate additional complexity. Together, these iterative enzymes orchestrate the efficient biosynthesis of elaborate natural products such as lovastatin, chaetoglobosin A, cytochalasin E, and aurovertin E.