Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein.
Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein.
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DOI：
10.1039/c5sc03864b
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发表时间：
2016-03-01
期刊：
影响因子：
8.4
通讯作者：
Crump MP
中科院分区：
文献类型：
--
作者：
Dong X;Bailey CD;Williams C;Crosby J;Simpson TJ;Willis CL;Crump MP
扩展的线性和环化的聚酮模拟物的合成和高分辨率的解决方案NMR结构被用来探测的放线菌紫素聚酮ACP与这些替代品的相互作用。聚酮化合物是一类具有重要药用和农用化学性质的次级代谢产物。生物合成是由聚酮酶（PKS）和酰基载体蛋白（ACP）进行的，ACP是一种小的酸性蛋白，它运输生长的聚酮链，对活性至关重要。在这里，我们报告的合成两个芳香族探针和线性octaketide模拟已拴到放线菌紫素ACP。这些实验旨在探测ACP螯合非极性相对于酚芳族环（其更接近地模拟聚酮化合物中间体）的能力以及用延长的聚酮化合物链替代物的研究。这些模拟物的结合已经使用高分辨率溶液NMR研究和高分辨率结构测定进行了评估。这些结果表明，令人惊讶的是，PKS ACP能够以脂肪酸型结合模式结合和螯合含有芳环的大体积非极性底物，但即使是很小程度的极性的引入也有利于在表面位点处显著不同的缔合，这与脂肪酸ACP所采用的缔合不同。
Extended linear and cyclised polyketide mimics were synthesized and high-resolution solution NMR structures were used to probe the interactions of the actinorhodin polyketide ACP with these surrogates. Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP's capacity to sequester a non-polar versus a phenolic aromatic ring (that more closely mimics a polyketide intermediate) as well as investigations with extended polyketide chain surrogates. The binding of these mimics has been assessed using high-resolution solution NMR studies and high-resolution structure determination. These results reveal that surprisingly a PKS ACP is able to bind and sequester a bulky non-polar substrate containing an aromatic ring in a fatty acid type binding mode, but the introduction of even a small degree of polarity favours a markedly different association at a surface site that is distinct from that employed by fatty acid ACPs.
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
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