Exobiology and Evolutionary Biology

PI: Huang, Faqing

Thioesters play essential roles in metabolism of modern organisms. It has been suggested that the importance of thioesters could have been traced back to the early stages of evolution, e.g., the RNA world. Supported by NASA’s Exobiology program, we have successfully isolated a number of ribozymes that can catalyze the syntheses of CoA, thioesters, and aminoacylated RNA from CoA thioesters. In this proposal research, I plan to construct an extensive ribozyme-based metabolic system that will have many of the salient features of contemporary metabolic pathways. The proposed ribo-metabolic system will have thioesters at its center and link different biological substrates and products (such as peptides and lipids) via catalytic activities of ribozymes. Proposed ribozyme activities will catalyze the syntheses of peptides and precursors to fatty acids and phospholipids from thioester building blocks. In addition, regulation of the ribometabolic system will be achieved through inhibition or activation of ribozyme activities by substrates, products, and/or other metabolic state indicators (such as ATP). In vitro selection techniques and synthetic chemistry will be employed to achieve the objectives. Results from this project will demonstrate that it is plausible not only to evolve ribozymebased metabolic systems but such systems are also capable of adapting to changes in their environments and metabolic states. The work may help define the probability of existence of ribo-organisms in a pre-protein era on earth or elsewhere in the universe and gain understanding on the metabolic complexity of such organisms. The proposed research therefore fits well within NASA’s second mission – To explore the Universe and search for life.