Aflatoxin and deconstruction of type I, iterative polyketide synthase function.
Aflatoxin and deconstruction of type I, iterative polyketide synthase function.
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DOI：
10.1039/c4np00092g
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发表时间：
2014-10
影响因子：
11.9
通讯作者：
Townsend CA
中科院分区：
文献类型：
--
作者：
Townsend CA
在这个观点中，重点是从深入分析黄曲霉毒素生物合成的多方面问题，已知的最高度重排的聚酮化合物天然产物之一。基本的化学见解已经出现到细胞色素P450介导的骨架重排如何发生通过可能的阳离子中间体和氧化脱芳构化，这是适用于更广泛的天然产物catenatization。因此，对于目前的实验方法在我们手中失败的地方，生物信息学工具和新的实验策略已经被开发出来，以识别大的多结构域蛋白质中的接头区域，并指导其组成部分的解剖和重组。已经可以推断出单个催化作用，如何协调整体合成以及如何以合理的方式重新设计这些酶以制备非天然产物。这些洞察力和创新往往不是计划或预期的，而是源于无法回答基本问题。科学的进步可能是偶然发生的，有利于有准备的头脑，其他时候则是拒绝放弃并设计新的解决方案来解决难题。这两条途径在研究黄曲霉毒素的生物合成过程中发挥了重要作用。对于这些贡献，我很高兴与约翰·维德拉斯和汤姆·辛普森分享这期NPR特刊，他们在世纪的最后三分之一中一直是这一领域的领导者。
In this viewpoint highlights are drawn from a deep analysis of the multifaceted problem of aflatoxin biosynthesis, one of the most highly rearranged polyketide natural products known. Fundamental chemical insights have emerged into how cytochrome P450-mediated skeletal rearrangements occur through probable cationic intermediates and oxidative dearomatizations, which are applicable more widely in natural product catabolism. So to where current experimental methods have failed in our hands, bioinformatic tools and fresh experimental strategies have been developed to identify linker regions in large, polydomain proteins and guide the dissection and reassembly of their component parts. It has been possible to deduce individual catalytic roles, how overall synthesis is coordinated and how these enzymes can be re-engineered in a rational manner to prepare non-natural products. These insights and innovations were often not planned or anticipated, but sprung from the inability to answer fundamental questions. Advances in science can take place by chance favoring the prepared mind, other times by refusing to give up and devising new solutions to address hard questions. Both ways forward played important roles in the investigation of aflatoxin biosynthesis. For these contributions I am pleased to share this special issue of NPR with John Vederas and Tom Simpson, who have been leaders in this field for the last third of a century.
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DOI：
10.1038/nrmicro2465
发表时间：
2010-12
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Nielsen MT;Nielsen JB;Anyaogu DC;Holm DK;Nielsen KF;Larsen TO;Mortensen UH
通讯作者：
Mortensen UH
影响因子：
3.2
作者：
Foulke-Abel, Jennifer;Townsend, Craig A.
通讯作者：
Townsend, Craig A.
DOI：
10.1073/pnas.0913531107
发表时间：
2010-04-06
影响因子：
11.1
作者：
Korman, Tyler Paz;Crawford, Jason M.;Tsai, Shiou-Chuan
通讯作者：
Tsai, Shiou-Chuan
DOI：
10.1039/c39820000206
发表时间：
1982-01-01
影响因子：
--
作者：
NAKASHIMA, TT;VEDERAS, JC
通讯作者：
VEDERAS, JC