(4bx) Biomolecular Engineering for Renewable Fuels and Chemicals

Fossil energy sources supply about 82% of US’s total energy need. While the total reserve of fossil resources is finite, the energy consumption grows at a stunning rate. Moreover, CO₂ produced from fossil fuel combustion has been implicated to contribute to climate changes. These reasons argue for an eventual replacement of fossil energy sources, which means that the fuels and chemicals must ultimately be produced from CO₂, H₂O, and sunlight. To this end, my doctoral work in Dr. James Liao’s group at UCLA was focusing on engineering of the biocatalysts to produce pharmaceutical intermediates, industrial commodities, and gasoline substitutes from a variety of renewable feed stocks.

i) A synthetic pathway has been designed to produce homophenylalanine, a core pharmaceutical intermediate, in Escherichia coli. To make this non-native chemical accessible to metabolic pathways, the key enzymes in carbon chain elongation and amination in E. coli were engineered by rational design and directed evolution. The carbon chain elongation platform demonstrated in this work could also be used to produce other non-native chemicals such as long chain alcohols. ii) Heterotrophic microbes such as E. coli utilize sugars as the feed stocks which are generated from plant biomass decomposition. To bypass plant biomass, photosynthetic chemical production was explored using the cyanobacterium Synechococcus elongatus. A synthetic pathway was installed in S. elongatus to produce 1,2-propanediol, an industrial commodity, directly from CO₂. The pathway was further tailored to match the special metabolic features in the photosynthetic organism. iii) The photosynthetic microbial process faces challenges in scaling-up due to the requirement of the light exposure surface area. To achieve light independent fuel and chemical production from CO₂, a lithoautotrophic microorganism Ralstonia eutropha was used. Metabolic engineering and electrochemical process design approaches were used to produce C4 and C5 alcohols, the gasoline substitutes, in an integrated electro-bioreactor using CO₂ as the sole carbon source and electricity as the sole energy input.

Taken together, biomolecular engineering may play a critical role in building of a sustainable society. Meanwhile, it is also one of my research interests to understand the universal chemical logic behind the versatile metabolic pathways, and the fundamental mechanisms of enzymatic catalysis. To further train myself in biochemistry and protein science, I will do my postdoc research in Dr. Peter Schultz’s group in the Scripps Research Institute. The ultimate goal would be to address some of the most interesting scientific and engineering challenges in renewable biomolecule synthesis using metabolic engineering, protein engineering, synthetic biology, bioinformatic, and process engineering approaches.