A Single Amino Acid Substitution Converts Benzophenone Synthase into Phenylpyrone Synthase*
A Single Amino Acid Substitution Converts Benzophenone Synthase into Phenylpyrone Synthase*
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单个氨基酸取代可将二苯甲酮合酶转化为苯基吡喃酮合酶*
DOI：
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发表时间：
2009
影响因子：
4.8
通讯作者：
L. Beerhues
中科院分区：
文献类型：
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作者：
T. Klundt;M. Bocola;Maren Lütge;T. Beuerle;Benye Liu;L. Beerhues
二苯甲酮代谢提供了许多植物天然产物，具有迷人的化学结构和有趣的药理活性。二苯甲酮合成酶(BPS)是由苯甲酰辅酶A和三个丙二酰辅酶A分子合成二苯甲酮类化合物的碳骨架，属于III型聚酮合成酶超家族的成员。活性部位空穴(T135L)的点突变将BPS转化为功能性苯基吡喃酮合成酶(PPS)。BPS底物和产物特性的巨大变化通过同源建模得到合理解释。该突变可能打开一个新的口袋，容纳三酮中间体的苯基部分，但将聚酮的延伸限制为两个反应，导致苯基吡喃酮的形成。3-羟基苯甲酰辅酶A是BPS的次佳起始分子，但不是PPS的底物。三酮中间体的芳基部分可能通过与主链形成氢键而被捕获在新的口袋中，从而起到抑制剂的作用。PPS是一种很有前途的生物技术工具，可用于操纵苯甲酸引发的生物合成途径，以产生新的化合物。
Benzophenone metabolism provides a number of plant natural products with fascinating chemical structures and intriguing pharmacological activities. Formation of the carbon skeleton of benzophenone derivatives from benzoyl-CoA and three molecules of malonyl-CoA is catalyzed by benzophenone synthase (BPS), a member of the superfamily of type III polyketide synthases. A point mutation in the active site cavity (T135L) transformed BPS into a functional phenylpyrone synthase (PPS). The dramatic change in both substrate and product specificities of BPS was rationalized by homology modeling. The mutation may open a new pocket that accommodates the phenyl moiety of the triketide intermediate but limits polyketide elongation to two reactions, resulting in phenylpyrone formation. 3-Hydroxybenzoyl-CoA is the second best starter molecule for BPS but a poor substrate for PPS. The aryl moiety of the triketide intermediate may be trapped in the new pocket by hydrogen bond formation with the backbone, thereby acting as an inhibitor. PPS is a promising biotechnological tool for manipulating benzoate-primed biosynthetic pathways to produce novel compounds.
影响因子：
--
作者：
Jez, JM;Austin, MB;Noel, JP
通讯作者：
Noel, JP
影响因子：
2.9
作者：
Jez, JM;Bowman, ME;Noel, JP
通讯作者：
Noel, JP