Sustainable Chemical Synthesis Inspired by Nature

   Research in the Chang Lab is interdisciplinary, aiming to harness the power of biological systems to solve outstanding problems at the frontiers of chemistry. Members of the lab leverage numerous techniques to design, probe, and optimize systems of reactions both in vivo and in vitro. These strategies encompass the burgeoning fields of synthetic biology, metabolic engineering, and biocatalysis, and are supported by studies in fundamental biochemistry and organic synthesis.

Exploring and expanding biocatalysis for non-canonical functional groups

   Advances in molecular biology in past decades have led to enzyme catalysis being of premier importance in sustainable chemical processes. However, the reaction space amenable to biocatalysis has been historically limited to simple hydrolysis and group transfer. Thus, we seek to develop biocatalytic methodology for incorporating functional groups which are rare in nature (eg. halogens, alkynes) but highly relevant to pharmaceuticals and chemical biology. These efforts are carried out by the biochemical characterization of novel enzymes, as well as engineering of known enzymes to improve their selectivity towards non-native substrates. By taking advantage of nature's catalysts, we aim to develop strategies for environmentally-friendly elaboration of chiral building blocks, natural product analogs, modified macromolecules, and other valuable specialty or commodity chemicals.

Sustainable chemical synthesis from carbon dioxide

   Diverse classes of organisms are able to biosynthesize all necessary cellular metabolites from carbon dioxide and sustainable energy sources by employing a number of unique carbon fixation pathways. Replicating these systems for targeted chemical synthesis has been a long-standing goal in the field of synthetic chemistry, owing to the abundance and low cost of carbon dioxide as a starting material. Additionally, the recent implication of carbon dioxide as a leading cause of anthropogenic climate change demonstrates the power of these sustainable synthesis platforms to transform an unwanted and harmful waste product into useful small molecule targets. Towards this goal, our lab investigates the transplantation of energy-efficient non-photosynthetic carbon fixation pathways into various hosts for the synthesis of value-added chemicals from carbon dioxide.

Engineering pathways for production of biofuels and biopolymers

   The growing global energy and plastic demand, coupled with concerns over climate change, have led to an escalating need to mine sustainable energy resources. One major source is the renewable carbon found in plant biomass, which can be converted to liquid fuels and sustainable polymers via microbial fermentation. We build new biosynthetic pathways in bacterial hosts that can convert plant biomass into fuel molecules (butanol, fatty acids etc.) and novel polymers (precursors for synthetic rubbers and nylons). Using methods of synthetic biology, we can draw enzymes from a variety of different environmental organisms and combine them in a single tractable host, followed by optimization of the pathway at various levels from enzyme sequence to host genome. This mix-and-match approach allows us to create and tailor new biological tools for multi-step, multi-enzyme sustainable chemical synthesis.

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