Curcuminoid Biosynthesis by Two Type III Polyketide Synthases in the Herb Curcuma longa
Curcuminoid Biosynthesis by Two Type III Polyketide Synthases in the Herb Curcuma longa
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DOI：
10.1074/jbc.m900070200
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发表时间：
2009-04-24
影响因子：
4.8
通讯作者：
Horinouchi, Sueharu
中科院分区：
文献类型：
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作者：
Katsuyama, Yohei;Kita, Tomoko;Horinouchi, Sueharu
姜黄素类化合物存在于姜黄（Curcuma longa）的根茎中，具有多种生物活性。尽管姜黄素类化合物的生物合成由于其药学上重要的性质和生物合成上有趣的结构而受到很多关注，但还没有阐明酶系统。在这里，我们提出了一个途径，姜黄素的生物合成中的草药C。longa，其包括两种新的III型聚酮酶。其中一种III型聚酮酶，称为二酮辅酶A合酶（DCS），通过缩合阿魏酰辅酶A和丙二酰辅酶A催化形成阿魏酰二酮辅酶A。另一个，命名为姜黄素合成酶（CURS），催化从肉桂酰二酮-N-乙酰半胱胺（CoA酯的模拟物）和阿魏酰CoA体外形成姜黄素类化合物。DCS和CURS在阿魏酰-CoA和丙二酰-CoA存在下的共孵育以高效率产生姜黄素，尽管CURS本身对于从阿魏酰-CoA和丙二酰-CoA合成姜黄素具有低活性。因此，这些发现揭示了姜黄中姜黄素的生物合成途径，其中DCS合成阿魏酰二酮-CoA，然后CURS将二酮-CoA酯转化为姜黄素类支架。
Curcuminoids found in the rhizome of turmeric, Curcuma longa, possess various biological activities. Despite much attention regarding the biosynthesis of curcuminoids because of their pharmaceutically important properties and biosynthetically intriguing structures, no enzyme systems have been elucidated. Here we propose a pathway for curcuminoid biosynthesis in the herb C. longa, which includes two novel type III polyketide synthases. One of the type III polyketide synthases, named diketide-CoA synthase (DCS), catalyzed the formation of feruloyldiketide-CoA by condensing feruloyl-CoA and malonyl-CoA. The other, named curcumin synthase (CURS), catalyzed the in vitro formation of curcuminoids from cinnamoyldiketide-N-acetylcysteamine (a mimic of the CoA ester) and feruloyl-CoA. Co-incubation of DCS and CURS in the presence of feruloyl-CoA and malonyl-CoA yielded curcumin at high efficiency, although CURS itself possessed low activity for the synthesis of curcumin from feruloyl-CoA and malonyl-CoA. These findings thus revealed the curcumin biosynthetic route in turmeric, in which DCS synthesizes feruloyldiketide-CoA, and CURS then converts the diketide-CoA esters into a curcuminoid scaffold.