Systematic investigation of the Escherichia coli metabolome for the biosynthetic origin of an isocyanide carbon atom
Systematic investigation of the Escherichia coli metabolome for the biosynthetic origin of an isocyanide carbon atom
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DOI：
10.1002/anie.200501942
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Clardy, J
中科院分区：
文献类型：
--
作者：
Brady, SF;Clardy, J
对天然产物生物合成的体内研究常常受到无法预测地控制生产生物体代谢组的阻碍。相反，当生物合成途径在被充分理解的模式生物中表达时，通过使用突变菌株可预测地控制代谢的能力允许对途径进行严格的检查，而这在野生型产生生物中是无法实现的。最近，我们从一个环境DNA （eDNA）克隆中分离并鉴定了含异氰酸酯的抗生素1及其生物合成基因（isnA和isnB）通过诱变编码初级代谢酶的基因系统地控制大肠杆菌代谢的能力，使我们能够阐明1中发现的异氰化物官能团的生物合成起源（方案1）。在第一个异氰化物官能化的天然产物黄索西林被发现近50年后，对异氰化物生物合成的广泛饲养研究中尚未出现一致的观点。[2,3]本文介绍了在1中发现的异氰化物基团的碳原子的来源。在大多数生物合成研究中，片段起源的线索可以从其结构中看到，而不是从唯一的碳原子中
In vivo studies on the biosynthesis of natural products are often hampered by the inability to predictably control the metabolome of the producing organism. In contrast, when biosynthetic pathways are expressed in well-understood model organisms, the ability to predictably control metabolism through the use of mutant strains allows pathways to be examined with a rigor that cannot be achieved in the wildtype-producing organism. Recently, we have described the isolation and characterization of the isocyanide-containing antibiotic 1 along with its biosynthetic genes (isnA and isnB) from an environmental DNA (eDNA) clone.[1] The ability to control Escherichia coli metabolism systematically through the mutagenesis of genes that code for primary metabolic enzymes has enabled us to elucidate the biosynthetic origin of the isocyanide functional group found in 1 (Scheme 1).Almost fifty years after the discovery of the first isocyanidefunctionalized natural product, xanthocillin, no consensus view of isocyanide biosynthesis has emerged from the extensive feeding studies that use isocyanide-producing organisms.[2, 3] The origin of the carbon atom of the isocyanide group found in 1 is presented herein. In most biosynthetic studies, a hint as to the origin of a fragment can be seen in its structure, but the lone carbon atom