Schröder J, Schröder G
Institute für Biologie II, Universität Freiburg, Bundesrepublik Deutschland.
Z Naturforsch C J Biosci. 1990 Jan-Feb;45(1-2):1-8. doi: 10.1515/znc-1990-1-202.
Several years of extensive research using the new powerful techniques of molecular biology have enabled the direct comparison of functionally or evolutionarily related genes and their products at the nucleotide and amino acid sequence levels. Two types of synthase with similar functions are discussed as an interesting example. Stilbene synthases, e.g. resveratrol synthase, produce the stilbene backbone as a key reaction in the biosynthesis of stilbene-type phytoalexins. Chalcone synthase is a key enzyme in the biosynthesis of flavonoids, including certain phytoalexins derived from a 6'-deoxychalcone which is synthesized by cooperation of chalcone synthase with a reductase. Resveratrol and chalcone synthases utilize the same substrates (4-coumaroyl-CoA and 3 molecules of malonyl-CoA) and catalyze the same condensing type of enzyme reaction (resulting in sequential addition of acetate units via malonyl-CoA), but the products differ in the newly formed ring systems (resveratrol and naringenin chalcone). A comparative analysis of cloned DNA sequences and of the reaction mechanisms indicates that the two enzymes are closely related. It seems likely that the proteins possess a common scaffold for substrate recognition and for the condensing reaction, and that the different folding of an enzyme-bound intermediate prior to closure of the new aromatic ring is responsible for the formation of the different products. The same type of condensing reaction is utilized by the 2-ketoacyl-ACP synthases of fatty-acid biosynthesis. However, the available data indicate that these enzymes share little overall homology with either resveratrol or chalcone synthase. One exception may be a short amino acid sequence which corresponds to the active center of the condensing reaction in 2-ketoacyl-ACP synthases.
数年以来，借助强大的分子生物学新技术开展的广泛研究，已能够在核苷酸和氨基酸序列水平上对功能相关或进化相关的基因及其产物进行直接比较。作为一个有趣的例子，我们讨论了两种功能相似的合酶。例如，芪合酶（如白藜芦醇合酶）在芪类植物抗毒素的生物合成中，催化生成芪骨架作为关键反应。查尔酮合酶是类黄酮生物合成中的关键酶，包括某些由查尔酮合酶与还原酶协同合成的6'-脱氧查尔酮衍生而来的植物抗毒素。白藜芦醇合酶和查尔酮合酶利用相同的底物（4-香豆酰辅酶A和3分子丙二酰辅酶A），并催化相同类型的缩合酶反应（通过丙二酰辅酶A依次添加乙酸单位），但产物在新形成的环系上有所不同（白藜芦醇和柚皮素查尔酮）。对克隆的DNA序列和反应机制的比较分析表明，这两种酶密切相关。蛋白质似乎拥有一个共同的支架，用于底物识别和缩合反应，并且在新芳香环闭合之前，酶结合中间体的不同折叠导致了不同产物的形成。脂肪酸生物合成中的2-酮酰基-ACP合酶也利用相同类型的缩合反应。然而，现有数据表明，这些酶与白藜芦醇合酶或查尔酮合酶几乎没有整体同源性。一个例外可能是一段短的氨基酸序列，它与2-酮酰基-ACP合酶缩合反应的活性中心相对应。
