文献类型：期刊文献

英文题名：Evolution of a Catalytic Mechanism

作者：Rauwerdink, Alissa[1,2];Lunzer, Mark[1,2];Devamani, Titu[1,2];Jones, Bryan[1,2];Mooney, Joanna[1,2];Zhang, Zhi-Jun[1,2,3];Xu, Jian-He[1,2,3];Kazlauskas, Romas J.[1,2];Dean, Antony M.[1,2,4,5]

机构：[1]Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA;[2]Univ Minnesota, Inst Biotechnol, Minneapolis, MN 55455 USA;[3]E China Univ Sci & Technol, Dept Biotechnol, Shanghai 200237, Peoples R China;[4]Univ Minnesota, Dept Ecol Evolut & Behav, Minneapolis, MN 55455 USA;[5]Sun Yat Sen Univ, Coll Ecol & Evolut, Guangzhou 510275, Guangdong, Peoples R China

年份：2016

卷号：33

期号：4

起止页码：971

外文期刊名：MOLECULAR BIOLOGY AND EVOLUTION

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000374226700009)】；

基金：This work was supported by the National Institute of Health (NIH) grant 5R01GM102205 and National Science Foundation (NSF) grant 1152804 to A.M.D. and R.J.K.

语种：英文

外文关键词：catalysis; transition state stabilization; gene duplication and divergence; escape from adaptive conflict; innovation; amplification; divergence

摘要：The means by which superfamilies of specialized enzymes arise by gene duplication and functional divergence are poorly understood. The escape from adaptive conflict hypothesis, which posits multiple copies of a gene encoding a primitive inefficient and highly promiscuous generalist ancestor, receives support from experiments showing that resurrected ancestral enzymes are indeed more substrate-promiscuous than their modern descendants. Here, we provide evidence in support of an alternative model, the innovation-amplification-divergence hypothesis, which posits a single-copied ancestor as efficient and specific as any modern enzyme. We argue that the catalytic mechanisms of plant esterases and descendent acetone cyanohydrin lyases are incompatible with each other (e.g., the reactive substrate carbonyl must bind in opposite orientations in the active site). We then show that resurrected ancestral plant esterases are as catalytically specific as modern esterases, that the ancestor of modern acetone cyanohydrin lyases was itself only very weakly promiscuous, and that improvements in lyase activity came at the expense of esterase activity. These observations support the innovation-amplification-divergence hypothesis, in which an ancestor gains a weak promiscuous activity that is improved by selection at the expense of the ancestral activity, and not the escape from adaptive conflict in which an inefficient generalist ancestral enzyme steadily loses promiscuity throughout the transition to a highly active specialized modern enzyme.