Research

Research Overview

Our group focuses on engineering biological systems to convert waste into value-added products, advancing the circular bioeconomy. We are particularly interested in one-carbon (C1) and two-carbon (C2) compounds as feedstock, which can be generated from valorization of gaseous wastes (CO2 and methane) and deconstruction of solid wastes (food, agricultural, and plastic wastes). We harness enzymes' remarkable capability to catalyze carbon-carbon (C-C) coupling reactions at ambient conditions without toxic or rare metals, transforming these simple building blocks into valuable chemicals.

Natural metabolic pathways for C1 and C2 assimilation are highly complex and tightly regulated, often resulting in carbon and energy inefficiencies when producing value-added compounds. To overcome these limitations, we develop synthetic pathways using new-to-nature C-C coupling enzymes that directly convert C1 and C2 substrates into multi-carbon products, bypassing host metabolism and its regulatory constraints.

Our research focuses on two key enzyme classes:

1. 2-hydroxyacyl-CoA synthase (HACS): Catalyzes acyloin condensation between carbonyl compounds (aldehydes/ketones) and formyl-CoA
2. 3-ketoacyl-CoA thiolase: Performs non-decarboxylative Claisen condensation between acyl-CoA molecules

By combining these CoA-dependent reactions, we create diverse functionalized compounds serving as precursors for fuels, polymers, and natural products. We employ enzyme mining, protein engineering, and high-throughput screening to optimize pathway development.

Fundamental biomanufacturing challenges—including low conversion yields and poor scalability—stem from conflicting objectives between cellular growth and engineered biosynthesis. The tight integration of carbon metabolism, energy metabolism, and biosynthetic pathways intensifies this competition.

Our group addresses these challenges through:

1. Temporal decoupling: Using dynamic gene expression to separate growth and production phases
2. Spatial decoupling: Compartmentalizing orthogonal pathways to isolate biosynthesis from host metabolism
3. Hybrid catalysis: Interfacing sustainable electro- and thermocatalysis with bioconversion, harnessing carbon-free electricity to power biosynthetic reactions

These strategies aim to develop stable and scalable microbial biocatalysts and bioprocesses that achieve carbon- and energy-efficient bioconversion of waste molecules into valuable products, advancing sustainable biomanufacturing technologies.