Paul Natasha, Joyce Gerald F
Departments of Chemistry and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12733-40. doi: 10.1073/pnas.202471099. Epub 2002 Sep 18.
A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 min(-1), whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 x 10(-11) M.min(-1). Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication.
一种自我复制分子指导组成分子的共价组装，以形成与母体组成相同的产物。当新形成的产物也能够指导产物分子的组装时，该自我复制系统可称为自催化的。基于一种核酶开发了一种自我复制系统，该核酶通过RNA催化的RNA连接反应催化自身额外拷贝的组装。对R3C连接酶核酶进行了重新设计，使其能够连接两个底物以生成自身的精确拷贝，然后该拷贝将以类似方式发挥作用。这种自我复制系统依赖于RNA的催化性质来生成拷贝。观察到新拷贝形成的初始速率与核酶的起始浓度之间呈线性关系，这与指数增长一致。自催化速率常数为0.011 min⁻¹，而在没有预先存在的核酶的情况下，初始反应速率仅为3.3×10⁻¹¹ M·min⁻¹。然而，指数增长是有限的，因为新形成的核酶分子与两个底物形成有效复合物的难度更大。对该系统的进一步优化可能会导致进行自我复制的核酶持续指数增长。
