Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis
Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis
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DOI：
10.1038/11553
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发表时间：
1999-08-01
期刊：
影响因子：
--
通讯作者：
Noel, JP
中科院分区：
文献类型：
--
作者：
Ferrer, JL;Jez, JM;Noel, JP
查耳酮合成酶（CHS）是植物中类黄酮抗微生物植物抗毒素和花青素色素生物合成的关键，它通过将一个对香豆酰-和三个丙二酰-辅酶A硫酯缩合成环化的聚酮反应中间体产生查耳酮，单独的CHS和与底物和产物类似物复合的CHS的晶体结构揭示了活性位点结构，其定义了多重脱羧的序列和化学性质，与白藜芦醇复合的CHS的结构还表明芪合酶（一种相关酶）如何使用相同的底物和替代的环化途径来形成白藜芦醇。通过使用CHS样序列的三维结构和大型数据库，我们可以鉴定可能具有新底物和产物特异性的蛋白质。该结构阐明了植物聚酮生物合成的化学基础，并为工程CHS样酶生产新产品提供了框架。
Chalcone synthase (CHS) is pivotal for the biosynthesis of flavonoid antimicrobial phytoalexins and anthocyanin pigments in plants, It produces chalcone by condensing one p-coumaroyl- and three malonyl-coenzyme A thioesters into a polyketide reaction intermediate that cyclizes, The crystal structures of CHS alone and complexed with substrate and product analogs reveal the active site architecture that defines the sequence and chemistry of multiple decarboxylation and condensation reactions and provides a molecular understanding of the cyclization reaction leading to chalcone synthesis, The structure of CHS complexed with resveratrol also suggests how stilbene synthase, a related enzyme, uses the same substrates and an alternate cyclization pathway to form resveratrol, By using the three-dimensional structure and the large database of CHS-like sequences, we can identify proteins likely to possess novel substrate and product specificity. The structure elucidates the chemical basis of plant polyketide biosynthesis and provides a framework for engineering CHS-like enzymes to produce new products.