Pentaketide resorcylic acid synthesis by type III polyketide synthase from Neurospora crassa
Pentaketide resorcylic acid synthesis by type III polyketide synthase from Neurospora crassa
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DOI：
10.1074/jbc.m701239200
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发表时间：
2007-05-11
影响因子：
4.8
通讯作者：
Horinouchi, Sueharu
中科院分区：
文献类型：
--
作者：
Funa, Nobutaka;Awakawa, Takayoshi;Horinouchi, Sueharu
III型聚酮酶（PKS）负责植物和细菌中芳香族聚酮的合成。丝状真菌的基因组分析已经预测了真菌III型PKS的存在，尽管迄今为止还没有功能特征。在粗糙脉孢菌（Neurospora crassa）的基因组中发现了一个开放阅读框架NCU 04801.1，它是一个新的Ⅲ型PKS，催化合成pentaketide烷基间苯二酚。NCU04801.1，因此命名为2 '-氧代烷基间苯二甲酸合酶（奥拉斯），优选硬脂酰-CoA作为起始底物，并缩合四个丙二酰-CoA分子以得到喷他肽中间体。对于奥拉斯以产生pentaketide烷基间苯二甲酸，中间体的羟醛缩合和芳构化（其仍然连接到酶上）可能随后水解以释放产物为间苯二甲酸。奥拉斯是第一个合成pentaketide resorcylic酸的III型PKS。
Type III polyketide synthases (PKSs) are responsible for aromatic polyketide synthesis in plants and bacteria. Genome analysis of filamentous fungi has predicted the presence of fungal type III PKSs, although none have thus far been functionally characterized. In the genome of Neurospora crassa, a single open reading frame, NCU04801.1, annotated as a type III PKS was found. In this report, we demonstrate that NCU04801.1 is a novel type III PKS catalyzing the synthesis of pentaketide alkylresorcylic acids. NCU04801.1, hence named 2'-oxoalkylresorcylic acid synthase (ORAS), preferred stearoyl-CoA as a starter substrate and condensed four molecules of malonyl-CoA to give a pentaketide intermediate. For ORAS to yield pentaketide alkylresorcylic acids, aldol condensation and aromatization of the intermediate, which is still attached to the enzyme, are presumably followed by hydrolysis for release of the product as a resorcylic acid. ORAS is the first type III PKS that synthesizes pentaketide resorcylic acids.