Initial characterization of a type I fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin B1

Initial characterization of a type I fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin B1
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DOI:
10.1016/s1074-5521(02)00213-2
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发表时间:
2002-09-01
影响因子:
--
通讯作者:
Townsend, CA
Townsend, CA
中科院分区:
生物1区
文献类型:
--
作者:
Watanabe, CMH;Townsend, CA

文献摘要

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强效环境致癌物黄曲霉毒素 B-1 的生物合成是由去甲茄酸合酶 (NorS) 启动的,NorS 是一种迭代 1 型聚酮化合物合酶和一对专门的酵母样脂肪酸合酶的复合物。 NorS 已从寄生曲霉中部分纯化,已发现其质量类似于 1.4 x 10(6) Da,并在乙酰辅酶 A、丙二酰辅酶 A 和 NADPH 存在下合成降索林酸,其中己酰辅酶 A 不是游离中间体。己酸的N-乙酰半胱胺硫酯可以替代HexA/B的催化功能,在仅丙二酰辅酶A存在的情况下引发复合物合成降索林酸。建议 NorS 的 α(2)β(2)gamma(2) 化学计量与其估计质量以及观察到的 PKS 和 FAS 酶的二聚体或高阶四级结构保持一致。
The biosynthesis of the potent environmental carcinogen aflatoxin B-1 is initiated by norsolorinic acid synthase (NorS), a complex of an iterative type 1 polyketide synthase and a specialized yeast-like pair of fatty acid synthases. NorS has been partially purified from Aspergillus parasiticus, has been found to have a mass of similar to1.4 x 10(6) Da, and carries out the synthesis of norsolorinic acid in the presence of acetylCoA, malonylCoA, and NADPH where hexanoyICoA is not a free intermediate. The N-acetylcysteamine thioester of hexanoic acid can substitute for the catalytic functions of HexA/B to initiate norsolorinic acid synthesis by the complex in the presence of only malonylCoA. An alpha(2)beta(2)gamma(2) stoichiometry is proposed for NorS in keeping with its estimated mass and the observed dimeric or higher-order quarternary structures of PKS and FAS enzymes.