Ribozyme-catalyzed amirloacylation from CoA thioesters

N Li
Faqing Huang, University of Southern Mississippi

Abstract

Coenzyme A (CoA) thioesters play essential roles in modern metabolism. To demonstrate plausible biochemical functions of thioesters in the RNA world, we have isolated a new class of ribozymes (ACT) that catalyze self-aminoacylation from a number of CoA thioesters with catalytic efficiencies ranging from 7000 to 24 000 M(-1.)min(-1). Active thioester substrates are required to contain both a free alpha-amino group in the acyl moiety and a CoA as the thiol component. We hypothesize ribozyme-based aminoacylation systems using aminoacyl thioesters of CoA as the ancestors of modern aminoacyl tRNA synthetases. On the basis of our previous results [Huang et al. (2000) Biochemistry 39, 15548-15555; Coleman and Huang (2002) Chem. Biol. 9, 1227-1236], an extensive RNA-catalyzed "metabolic pathway" involving CoA and its thioesters is proposed. Complex contemporary metabolic systems could have evolved from the proposed ribozyme pathways.