Total synthesis approaches to natural product derivatives based on the combination of chemical synthesis and metabolic engineering
Total synthesis approaches to natural product derivatives based on the combination of chemical synthesis and metabolic engineering
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DOI：
10.1039/b709549j
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Knobloch, Tobias
中科院分区：
文献类型：
--
作者：
Kirschning, Andreas;Taft, Florian;Knobloch, Tobias
次级代谢产物是一组极其多样和重要的天然产物，具有工业和生物医学意义。天然和异源次级代谢产物生产生物体的代谢工程的进展已经允许通过利用其生物合成潜力来定向合成所需的新产物。代谢工程利用细胞代谢的知识来改变生物合成途径。突变合成（mutational biosynthesis，MBS）是化学合成与代谢工程相结合的一项重要技术，它是在生物合成酶定向生物合成（PDB）的基础上发展起来的。这两种技术都是基于修饰的生物合成中间体的细胞摄取及其掺入复杂的次级代谢产物。突变合成利用基因工程生物体结合化学修饰的中间体的进料。从合成化学家的角度来看，突变合成的概念是非常有吸引力的，因为该方法将化学专业知识与自然的合成机制相结合，因此可以用于快速创建次级代谢产物的小型库。然而，在每种情况下，该方法必须严格地与半合成和全合成的实用性和效率进行比较。代谢工程的最新发展有望进一步扩大将化学要求高的步骤外包给生物系统的范围。
Secondary metabolites are an extremely diverse and important group of natural products with industrial and biomedical implications. Advances in metabolic engineering of both native and heterologous secondary metabolite producing organisms have allowed the directed synthesis of desired novel products by exploiting their biosynthetic potentials. Metabolic engineering utilises knowledge of cellular metabolism to alter biosynthetic pathways. An important technique that combines chemical synthesis with metabolic engineering is mutasynthesis ( mutational biosynthesis; MBS), which advanced from precursor-directed biosynthesis ( PDB). Both techniques are based on the cellular uptake of modified biosynthetic intermediates and their incorporation into complex secondary metabolites. Mutasynthesis utilises genetically engineered organisms in conjunction with feeding of chemically modified intermediates. From a synthetic chemist's point of view the concept of mutasynthesis is highly attractive, as the method combines chemical expertise with Nature's synthetic machinery and thus can be exploited to rapidly create small libraries of secondary metabolites. However, in each case, the method has to be critically compared with semi- and total synthesis in terms of practicability and efficiency. Recent developments in metabolic engineering promise to further broaden the scope of outsourcing chemically demanding steps to biological systems.