Michelle Chang

To reach Professor Chang during the Spring of 2024, please use this email: [email protected].

Biocatalysis, Natural Products Discovery, Chemical Biology, and Synthetic Biology — Designing new biosynthetic pathways for synthesis of small molecules

Our research laboratory works at the interface of enzymology and synthetic biology to address problems in human health and the environment. We are interested in the discovery, characterization, and engineering of new enzymes and biosynthetic pathways as an approach to develop new biocatalytic methods to generate molecular diversity and synthesize diverse small molecule targets. A unifying theme of our projects is a focus on gaining a detailed mechanistic understanding of how enzymes and metabolic pathways function to provide new avenues for engineering function.

Biocatalysis and enzyme mechanism

The ability to synthesize molecules of interest has transformed human society at many levels. Our lab is interested in taking advantage of the ability of enzymes to catalyze challenging reactions with high stereo- and site selectivity under mild conditions. We study metalloenzymes that carry out selective C-H activation chemistry to achieve a variety of downstream functionalization ranging from halogenation to addition of variety of other groups. Towards this goal, we are also interested in mechanistic studies that allow us to better understand how these unusual reactions work and to provide new insight into expanding their reaction scope. We are also interested in the discovery of new metalloenzymes and other enzymes that catalyze key transformations such as C-C bond or amide bond formation and engineering their use for biocatalysis and chemical biology applications.

Natural product discovery and engineering

Natural products and their scaffolds continue to provide a rich source for the discovery and development of new therapeutics. We are interested in the discovery of new biosynthetic pathways to access enzymes and small molecule scaffolds with new functional groups, architectures, and bioactivity. We have been specifically interested in engineering the production of fluorinated natural products as well as alkaloid natural products derived from amino acids. These pathways can then be engineered to produce both pharmacophores of interest, such as site selectively modified heterocycles, as well as to provide more complex modified peptides and proteins for bio-orthogonal chemistry.

Synthetic biology

Living systems have solved many important challenges in chemistry, ranging from carbon and nitrogen fixation to the degradation of waste. Our group is interested in the metabolic engineering of different cell processes in order to carry out chemical synthesis in living cells by microbial fermentation. We have focused on engineering pathways for biofuel and biodegradable plastic in living cells as well as those for assimilation of carbon dioxide via non-photosynthetic carbon fixation.