Molecular biology - Making catalytic DNAs
Molecular biology - Making catalytic DNAs
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DOI：
10.1126/science.290.5499.2095
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发表时间：
2000-12-15
期刊：
影响因子：
56.9
通讯作者：
Breaker, RR
中科院分区：
文献类型：
--
作者：
Breaker, RR
大自然用了超过 30 亿年的时间来完善活细胞中发现的数千种酶。然而，这种漫长而无情的进化过程已经产生了仅基于两种分子形式的酶——蛋白质和RNA。但是，在追求催化完美的过程中，进化可能并未充分利用所有可用的分子形式来构建酶。最近，酶工程师创造了一种称为脱氧核酶的 DNA 分子，它具有类似酶的特性。鉴于 DNA 对细胞的重要性，这些工程 DNA 酶可能具有相当大的实际用途。 在选择用蛋白质和 RNA 构建生物催化剂时，大自然做出了两个绝佳的选择。蛋白质利用其 20 种氨基酸所提供的不同化学性质，形成一系列令人难以置信的多样化结构和精确配置的活性位点。蛋白质令人惊叹的催化潜力以酶为例，例如乳清苷 5'-磷酸脱羧酶，它将底物转化为产物，其速率比相应的未催化速率提高了 17 个数量级 (1)。 RNA 还可以通过形成令人惊讶的复杂三维结构，将其较少的化学成分发挥到催化作用 (2-4)。尽管 RNA 在现代生物催化中的作用可能是生命早期进化历史中的一个保留 (5)，但催化 RNA（核酶）确实能够产生令人印象深刻的速率增强。例如，I 组核酶催化 RNA 剪接，速率提高约 13 个数量级。迄今为止，仅鉴定出八种不同类别的天然存在的 RNA 生物催化剂，但大自然对 RNA 的催化能力极为信任 - 核糖体是指导所有细胞中蛋白质合成的复杂 RNA-蛋白质工厂，其核心有一种 RNA 酶 (6, 7)。
Nature has had more than 3 billion years to perfect the many thousands of enzymes that are found in living cells. Yet this long and unforgiving process of evolution has given rise to enzymes based on only two molecular formats—protein and RNA. But, in its quest for catalytic perfection, evolution may not have fully exploited all available molecular formats for enzyme construction. Recently, enzyme engineers have created DNA molecules called deoxyribozymes that have enzyme-like properties. Given the importance of DNA to the cell, these engineered DNA enzymes could have considerable practical use.In opting to build biocatalysts from protein and RNA, nature has made two excellent choices. Proteins exploit the different chemistries offered by their constituent 20 amino acids to form an incredible array of diverse structures and precisely configured active sites. The awesome catalytic potential of proteins is exemplified by enzymes, such as orotidine 5'-phosphate decarboxylase, which converts substrate to product with a rate enhancement of 17 orders of magnitude over the corresponding uncatalyzed rate (1). RNA also can bring its lesser chemical repertoire to bear on catalysis by forming surprisingly intricate three-dimensional structures (2–4). Although RNA's job in modern biocatalysis might be a holdout from life's early evolutionary history (5), catalytic RNAs (ribozymes) are certainly capable of generating impressive rate enhancements. For example, group I ribozymes catalyze RNA splicing with a rate enhancement of∼ 13 orders of magnitude. Only eight distinct classes of naturally occurring RNA biocatalysts have been identified so far, yet nature is extraordinarily trusting of RNA's catalytic prowess—the ribosome, the complex RNA-protein factory that guides protein synthesis in all cells, has an RNA enzyme at its core (6, 7).