Understanding and reprogramming nature’s biosynthetic machinery

Our research projects span a broad range of topics, incluing mechanistic enzymology, structural biology, chemical biology, synthetic biology, biocatalysis, and biomaterials.

Welcome to the Hai research group

Nature manufactures a large number of complex molecules, ranging from biologically active natural products to structurally diverse biopolymers, by using its exquisite protein machinery. These biosynthetic enzymes are not only elegantly evolved to catalyze challenging chemical transformations, but also are intricate nano-machines programmed to assemble the desired products in a highly efficient manner. Understanding how individual biosynthetic enzymes perform catalysis, and how these protein machines are coordinated and regulated, is essential for the emerging synthetic biology field to fully harness nature’s synthetic potential. Our ultimate goal is to understand and reprogram these biosynthetic protein machines for the synthesis of medicinally and industrially important molecules. Toward this goal, we use a multifaceted approach, combining chemical biology, structural biology, enzymology, genetics, and bioinformatics to answer the following questions:

  • What are the enzyme mechanisms and what are the molecular determinants for the substrate specificity and reaction selectivity?
  • How do we discover new enzyme functions and expand the biocatalytic toolbox by leveraging the ever-expanding genomic data?
  • Can we diversify and create new enzyme functions guided by our knowledge on protein structure-function relationship?
  • What are nature’s strategies for complex molecule construction? Can we design artificial pathways to synthesize products of unnatural origin?

Enzymology & chemical biology

We use combined methods and techniques from biochemistry, biophysics, chemical and structural biology to study enzyme function, mechanism, and structure. We are particularly interested in discovering new enzymes through a genome mining approach.

Biosynthesis & synthetic biology

Enzymes involved in natural product biosynthesis are capable of carrying out challenging chemical transformations in a stereospecific manner. We will leverage our expertise in enzymology to engineer these enzymes in order to harness their synthetic potentials.

Biomolecular tools & materials

We develop synthetic biological approaches for the synthesis of functional biopolymers and other biomaterials in collaboration with experts in materials science on campus. We are also interested in developing protein/peptide-based imaging tools and sensors for application in health, environmental protection, agriculture and food safety.

Click here for ongoing projects

Currently, we focus on studying biosynthetic enzymes synthesizing and modifying non-canonical amino acids and peptides.

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