Thulasiram Hirekodathakallu V, Erickson Hans K, Poulter C Dale
Department of Chemistry, University of Utah, 315 South 1400 East, Room 2020, Salt Lake City, UT 84112, USA.
Science. 2007 Apr 6;316(5821):73-6. doi: 10.1126/science.1137786.
The carbon skeletons of over 55,000 naturally occurring isoprenoid compounds are constructed from four fundamental coupling reactions: chain elongation, cyclopropanation, branching, and cyclobutanation. Enzymes that catalyze chain elongation and cyclopropanation are well studied, whereas those that catalyze branching and cyclobutanation are unknown. We have catalyzed the four reactions with chimeric proteins generated by replacing segments of a chain-elongation enzyme with corresponding sequences from a cyclopropanation enzyme. Stereochemical and mechanistic considerations suggest that the four coupling enzymes could have evolved from a common ancestor through relatively small changes in the catalytic site.
超过55000种天然存在的类异戊二烯化合物的碳骨架由四种基本偶联反应构建而成：链延长、环丙烷化、分支和环丁烷化。催化链延长和环丙烷化的酶已得到充分研究，而催化分支和环丁烷化的酶尚不清楚。我们通过用环丙烷化酶的相应序列替换链延长酶的片段所产生的嵌合蛋白催化了这四种反应。立体化学和机理方面的考虑表明，这四种偶联酶可能通过催化位点相对较小的变化从一个共同祖先进化而来。
