Ongoing Projects

Current Projects and Partnerships at the Hai Group

Structure-Function Study of PLP-Dependent Enzymes

Pyridoxal-5’-phosphate (PLP)-dependent enzymes are able to catalyze a diverse range of chemical transformations involving amino acids and their derivatives. The remarkable catalytic versatility of PLP-dependent enzymes renders them as promising biocatalysts in asymmetric synthesis of chiral amino acid building blocks. We focus on discovering new PLP-dependent enzymes involved in natural product biosynthesis and developing them into biocatalysts for non-canonical amino acid biosynthesis.

Template-independent enzymatic polymerization

Nature makes an incredible array of biopolymers such as rubber (polyisoprene), cellulose (polycarbohydrates), and polyhydroxybutyrate (polyester) in a template-independent fashion. Despite their prevalent application as biomaterials and renewable energy sources in various fields, the underlying molecular mechanism by which they are synthesized in nature have just begun to be understood. We are investigating the biosynthesis of an array of polyamides. Our goal is to understand the underlying molecular mechanism regarding how enzyme machinery controls chain initiation (priming), chain elongation (processivity and directionality), and chain termination (chain length determinants). We aim to engineer these enzymes to make new biopolymers and leverage our mechanistic understanding to discover new biopolymers in nature using a genome-mining approach.

Post-translationally modifying enzymes

Peptidyl arginine deiminase (PADs) are responsible for protein citrullination, an important protein post-translational modification (PTM) which irreversibly converts a positively charged arginine residue into a neutral citrulline residue. Hence, protein citrullination can dramatically alter protein structure and function, and is involved in a myriad of cellular events. It has been shown that PADs play important regulatory role and are implicated in many diseases, such as carcinogenesis and autoimmune inflammatory diseases. By far PAD6 is the least-understood member of the PAD family in mammals although genetic studies have shown that PAD6 is essential for oocyte cytoskeletal sheet formation and female fertility. We are using an integrated approach combining structural biology and chemical biology to unravel its function.

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