Chemical Engineering Seminar
Aditya is from Houston, Texas, and interned for 5 summers with Shell and ExxonMobil during his undergraduate years. His interest in biomolecular engineering was sparked by a desire to develop renewable liquid transportation fuel alternatives, and he is always excited to discover what chemicals can be formed from renewable sources using biocatalysis. During his post-doc, he became fascinated by the enormous potential and creative opportunities to harness designer bacteria for biomedical applications. Whether for healthcare or sustainability purposes, Aditya is most interested in adding new functional group chemistries to metabolites and proteins. When outside of lab, Aditya enjoys playing board games, watching basketball/football, and traveling. The goal of our lab is to use synthetic biology approaches to investigate how microbes can use non-standard chemistry and unusual building blocks to generate products that exhibit enhanced functionality. Products of interest include fuels, chemicals, materials, and therapeutics. Example questions of interest are: What useful functional groups can we generate on small molecules and proteins using enzymatic catalysis and metabolic engineering? Will small molecules containing unusual functional groups be orthogonal to endogenous cellular processes, will they be consumed by the cell, or will they be toxic? Will these molecules be able to enter/exit cells? How might we engineer cells to overcome potential challenges with orthogonality, toxicity, or transport? Can we use non-standard amino acid incorporation to advance rational modification of enzyme active sites and protein binding pockets? Advancements in synthetic biology, genome engineering, and intelligent screening enable us to efficiently determine answers to these questions.
Diverse challenges in human and environmental health can be addressed by harnessing the power of biocatalysis to create unnatural building block chemicals - efficiently, selectively, and potentially in distributed contexts by autonomous cells. Our lab is expanding the biological repertoire of building blocks by engineering metabolism, proteins, and genomes. In this talk, I will present glimpses of our work in three related research directions. First, we have designed biochemical routes to add amine functionality to carboxylic acids and aldehydes derived from plastic or biomass waste. Our mono- and diamine monomers should allow for polymer upcycling. Second, we are advancing the biosynthesis of non-standard amino acids (nsAAs) by live cells, with an emphasis on introducing heteroatom functionality onto aromatic amino acid sidechains. One example is the biosynthesis of an immunogenic amino acid that contains a nitroaromatic sidechain. We demonstrate the design of live bacterial cells that biosynthesize para-nitro-L-phenylalanine and that insert it within specific sites of target proteins. This technology may serve as a foundation for live bacterial vaccines that produce recombinant antigens for better recognition by the immune system. To enable a more generalizable approach to nsAA biosynthesis for diverse applications, we also report new and improved
members of an enzyme family that produces diverse beta-hydroxylated aromatic amino acids from aromatic aldehyde precursors. Finally, I will briefly discuss the ability to use unnatural building blocks for biological containment of engineered microbes. The ability to effectively contain engineered microbes through engineered dependency on unnatural building blocks could unlock the potential of microbial synthetic biology for use in the field. Here, I review our published efforts in designing effective containment for E. coli strains.