Benzalacetone synthase -: A novel polyketide synthase that plays a crucial role in the biosynthesis of phenylbutanones in Rheum palmatum
Benzalacetone synthase -: A novel polyketide synthase that plays a crucial role in the biosynthesis of phenylbutanones in Rheum palmatum
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DOI：
10.1046/j.1432-1327.2001.02255.x
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发表时间：
2001-06-01
期刊：
影响因子：
--
通讯作者：
Noguchi, H
中科院分区：
文献类型：
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作者：
Abe, I;Takahashi, Y;Noguchi, H
苄叉丙酮合酶（BSA）是一种植物特异性的聚酮合酶，能催化4-香豆酰辅酶A与丙二酰辅酶A一步脱羧缩合生成苯丁酸类化合物的C-6-C-4骨架。首次从药用植物大黄（Rheumpalmatum）中克隆到一个编码BAS的cDNA并进行了序列测定。该cDNA编码一个42 kDa的蛋白质，与CHS超家族酶的其他成员共享60-75%的氨基酸序列同一性。有趣的是，R。掌叶菊BAS缺乏活性位点Phe 215残基（在CHS中编号），该残基被提出在CHS中4-香豆酰-CoA与丙二酰-CoA的顺序缩合期间帮助定向底物和中间体。另一方面，CHS中的催化半胱氨酸-组氨酸二联体（Cys 164-His 303）在BAS中是很保守的。在大肠杆菌中表达的重组酶有效地从4-香豆酰-CoA和丙二酰-CoA得到苄叉丙酮作为单一产物。此外，与显示出对脂肪族辅酶A酯的广泛底物特异性的CHS相反，BAS不接受己酰辅酶A、异丁酰辅酶A、异戊酰辅酶A和乙酰辅酶A作为底物。最后，除了大黄中的苯基丁酮外，BAS已被提出在多种天然产物的C-6-C-4部分的构建中起关键作用，例如生姜植物中具有药用重要性的姜辣素。
Benzalacetone synthase (BSA) is a novel plant-specific polyketide synthase that catalyzes a one step decarboxylative condensation of 4-coumaroyl-CoA with malonyl-CoA to produce the C-6-C-4 skeleton of phenylbutanoids in higher plants. A cDNA encoding BAS was for the first time cloned and sequenced from rhubarb (Rheum palmatum), a medicinal plant rich in phenylbutanoids including pharmaceutically important phenylbutanone glucoside, lindleyin. The cDNA encoded a 42-kDa protein that shares 60-75% amino-acid sequence identity with other members of the CHS-superfamily enzymes. Interestingly, R. palmatum BAS lacks the active-site Phe215 residue (numbering in CHS) which has been proposed to help orient substrates and intermediates during the sequential condensation of 4-coumaroyl-CoA with malonyl-CoA in CHS. On the other hand, the catalytic cysteine-histidine dyad (Cys164-His303) in CHS is well conserved in BAS. A recombinant enzyme expressed in Escherichia coli efficiently afforded benzalacetone as a single product from 4-coumaroyl-CoA and malonyl-CoA. Further, in contrast with CHS that showed broad substrate specificity toward aliphatic CoA esters, BAS did not accept hexanoyl-CoA, isobutyryl-CoA, isovaleryl-CoA, and acetyl-CoA as a substrate. Finally, besides the phenylbutanones in rhubarb, BAS has been proposed to play a crucial role for the construction of the C-6-C-4 moiety of a variety of natural products such as medicinally important gingerols in ginger plant.