Dr. Arthur Weber

Curriculum Vitae:

What were the chemical processes that started life on Earth? Biochemist Art Weber is trying to answer this question by studying prebiotically plausible chemical reactions in the lab – reactions that might have been responsible for biogenesis.

Art’s experiments have shown that sugars are unsurpassed in their ability to undergo spontaneous self-transformation reactions in water. Consequently, for the past decade he’s been investigating the prebiotic synthesis of sugars and their subsequent reactions in the presence of ammonia that yield a complex mixture of chemical products whose activities are essential to the origin of life, and even combine to form semi-solid microspherules that could have provided a primitive cell-like, catalytic environment. The ultimate goal of his research effort is to develop a model, self-replicating system that resembles the birth of life on Earth, and can be artificially evolved to a more dynamic and complex state.

Projects

Prebiotic Synthesis of Autocatalytic and Self-Replicating Molecules from Sugars as the Primary Carbon Source

NNX08AP48A

Our research objective is to understand and model the chemical processes on the primitive Earth that generated the first autocatalytic molecules and microstructures involved in the origin of life. Our approach involves (a) investigation of a model origin-of-life process named the Sugar Model that is based on the reaction of formaldehyde-derived sugars with ammonia and amines (60, 62), and (b) elucidation of the constraints imposed on the chemistry of the origin of life by the fixed energies and rates of aliphatic organic reactions under mild aqueous conditions (59, 61, 63, 64). As shown earlier in Figure 1, the Sugar Model is a plausible “one-pot” prebiotic process that converts very simple substrates (formaldehyde, glycolaldehyde, ammonia, and hydrogen sulfide) to a variety of products: small catalytic molecules, “energy-rich” thioesters and phosphoanhydrides. More recently we showed (a) that homochiral amines (like amino acids and peptides) catalyze the stereoselective synthesis of tetrose sugars from glycolaldehyde, and (b) that sugar-amine (or ammonia) reactions generate semi-solid organic microspherules, and crude product mixtures with autocatalytic activity. Here we propose to investigate four aspects of the Sugar Model chemistry labeled A-D in Figure 1 shown earlier that are relevant to central questions about the origin of life: (A) the origin of biohomochirality by examining stereoselective sugar synthesis using homochiral peptide (amine) catalysts, (B) the origin of autocatalytic protocells by incorporating catalytic groups into the molecular matrix of organic microspherules that would give them the ability to internally catalyze their own synthesis, (C) the origin of molecular replication by examining the prebiotic synthesis and hydrogen-bonding properties of “nucleic acid-like” complementary pyrazines from sugar-amine (ammonia) reactions, and (D) the origin of ammonia biosynthesis by investigating the sugar-driven reduction of nitrite (nitrate) to ammonia. In addition, we would extend our studies of the thermodynamics (energies) and kinetics (rates) of organic transformations to nitrogen-containing aliphatic organic molecules in order to develop a better understanding of the chemical constraints that governed the origin of life and its metabolism. In the first year we plan to focus our research effort on Sugar Model aspects (A)-20% time, (B)-40% time, and (C)-40% time with studies of area (D) and organic reaction rates beginning in the second year.