Wendt KU, Schulz GE, Corey EJ, Liu DR
Institut für Organische Chemie und Biochemie Albertstrasse 21, 79104 Freiburg (Germany).
Angew Chem Int Ed Engl. 2000 Aug 18;39(16):2812-2833.
The mechanisms by which triterpene cyclases transform olefins into complex and biologically important polycyclic products have fueled nearly half a century of intense research. Recent chemical and biological studies, together with previous findings, provide intriguing new insights into the enzymatic mechanism of triterpene formation and form a surprisingly detailed picture of these elegant catalysts. It can be concluded that the role of the oxidosqualene cyclases involves protection of the intermediate carbocation against addition of water or deprotonation by base, thereby allowing the shift of the hydride and methyl groups along a thermodynamically and kinetically favorable cascade. Key questions in the areas of structural biology, site-directed mutagenesis, and directed evolution are apparent, now that the first structure of a triterpene cyclase is known.
三萜环化酶将烯烃转化为复杂且具有生物学重要性的多环产物的机制推动了近半个世纪的深入研究。最近的化学和生物学研究，以及先前的发现，为三萜形成的酶促机制提供了有趣的新见解，并形成了这些精妙催化剂令人惊讶的详细图景。可以得出结论，氧化鲨烯环化酶的作用涉及保护中间碳正离子免受水的加成或碱的去质子化，从而使氢化物和甲基沿着热力学和动力学有利的级联反应发生转移。鉴于三萜环化酶的首个结构已为人所知，结构生物学、定点诱变和定向进化领域的关键问题显而易见。
