Enzymatic Synthesis of Optically-active Selenium and Tellurium Containing Amino Acids and the Reaction Mechanism

自然界中存在多种含硒氨基酸，其中大部分具有生理活性。本研究以多功能吡哆醛-P酶为原料，制备了化学合成难度较大的光学活性含硒氨基酸，并对酶促反应的机理进行了探讨。我们获得的结果如下：(1)合成了含碲氨基酸，有望作为胰腺的特异性显像剂。(2)利用细菌L蛋氨酸裂解酶和酵母菌O-乙酰高丝氨酸(硫醇)裂解酶，以硒醇和廉价氨基酸为原料，合成了多种光学活性的含硒氨基酸。由于这两种酶不仅催化~lt；β&gt；，而且还催化~lt；γ&gt；-取代反应，所以我们不仅可以合成硒取代的L硒半胱氨酸，还可以合成硒取代的L硒同型半胱氨酸。O-乙酰高丝氨酸(硫醇)裂解酶只催化取代反应。因此，与L蛋氨酸裂解酶相比，合成反应进行得更有效。(3)然而，我们发现包埋在聚氨酯中的L蛋氨酸裂解酶只催化取代反应，而且修饰后的酶实际上是合成硒氨基酸的有效生物催化剂。(4)我们还开发了一种新的合成方法，利用细菌色氨酸合成酶合成具有光学活性的含硒氨基酸。

Various selenium-containing amino acids occur in nature, and most of them are physiologically active. The present study has been undertaken to prepare optically active selenium-containing amino acids, which are synthesized chemically with great difficulty, with multi-functional pyridoxal-P enzymes, and also to clarify the mechanism of the enzymatic reactions. The results that we have obtained are as follows.(1) We have synthesized tellurium-containing amino acids, which are expected to be useful as a specific imaging agent for pancreas. Te-Phenyl-L-tellurohomocysteine and Te-phenyl-L-tellurocysteine have been synthesized.(2) Various optically-active selenium-containing amino acids have been obtained from selenols and cheaply-available amino acids with bacterial L-methionine <gamma> -lyase and yeast O-acetylhomoserine(thiol)-lyase. As both the enzymes catalyze not only <beta> but also <gamma> -replacement reactions, we could synthesize not only Se-substituted-L-selenocysteine but Se-substituted-L-selenohomocysteine. O-Acetylhomoserine(thiol)-lyase catalyzes only replacement reactions. Therefore, the synthetic reactions proceed efficiently in contrast with that with L-methionine <gamma> -lyase which catalyzes elimination reactions in addition to replacement reactions.(3) However, we have found that L-methionine <gamma> -lyase entrapped in polyurethane catalyzes only replacement reactions, and that the modified enzyme works actually as an efficient biocatalyst for the synthesis of selenium amino acids.(4) We have also developed a novel synthetic procedure for optically-active selenium-containing amino acids with bacterial tryptophan synthase, which inherently functions in the tryptophan synthesis.