Research

Genome engineering for non-model microorganisms

Many non-model microorganisms have valuable natural capabilities but lack the genetic tools available for common laboratory organisms. We develop genome-engineering tools to study and engineer these microbes, creating a foundation for useful applications.

Our work includes CRISPR-Cas9, CRISPR-Cpf1, and CRISPR interference systems, as well as approaches that harness microorganisms’ own CRISPR-Cas machinery. These tools enable targeted genome modifications and control of gene expression.

Building on a foundation in Clostridium, we have extended genome-engineering toolkits to microorganisms relevant to agriculture and the environment, including Bacillus, Bradyrhizobium, methanotrophs, and aquaculture-associated bacteria.

For biomanufacturing applications, we pair genome engineering with metabolic and protein engineering and evaluate strains through fermentation and product-recovery studies. This links molecular changes to the behavior of biological production systems.

Relevant publications

• High-Efficiency CRISPR-Cas9 Genome Editing Unveils Biofilm Insights and Enhances Antimicrobial Activity in Bacillus velezensis FZB42. Biotechnology and Bioengineering (2025).
• High-Efficiency Genome Editing in Naturally Isolated Aeromonas hydrophila and Edwardsiella piscicida Using the CRISPR-Cas9 System. Biotechnology and Bioengineering (2025).
• Exploiting endogenous CRISPR-Cas system for multiplex genome editing in Clostridium tyrobutyricum and engineer the strain for high-level butanol production. Metabolic Engineering (2018).
• Multiplexed CRISPR-Cpf1-Mediated Genome Editing in Clostridium difficile toward the Understanding of Pathogenesis of C. difficile Infection. ACS Synthetic Biology (2018).
• Bacterial Genome Editing with CRISPR-Cas9: Deletion, Integration, Single Nucleotide Modification, and Desirable “Clean” Mutant Selection in Clostridium beijerinckii as an Example. ACS Synthetic Biology (2016).
• Gene transcription repression in Clostridium beijerinckii using CRISPR-dCas9. Biotechnology and Bioengineering (2016).

Metabolic engineering for renewable bioproducts

We redesign microbial metabolism and bioprocesses to produce renewable fuels, chemicals, materials, and other useful bioproducts. Our approach integrates microbial host selection, pathway engineering, and bioprocess development to advance sustainable biomanufacturing, from strain design to efficient production and downstream product recovery.

Our published work has demonstrated record-setting production levels of n-butanol, fatty acid esters, and hexanoic acid in engineered microbial hosts, alongside advances in other renewable bioproducts. We have also established an anaerobic Clostridium platform for recombinant protein production.

Our fatty acid ester research illustrates how metabolic design can enable high-value products to be recovered more easily from fermentation broth. We continue to develop microbial production platforms that connect biological performance with practical biomanufacturing needs.

Relevant publications

• Metabolic engineering of Clostridium tyrobutyricum for hexanoic acid and hexanol production. Bioresource Technology (2026).
• Deciphering D-2,3-Butanediol Metabolic Pathways in a Newly Isolated Bacillus velezensis and Rationally Engineering Bacillus subtilis for Efficient Production of Optically Pure D-2,3-Butanediol. ACS Synthetic Biology (2025).
• Development of an Efficient Recombinant Protein Expression System in Clostridium saccharoperbutylacetonicum Based on the Bacteriophage T7 System. ACS Synthetic Biology (2023).
• Renewable fatty acid ester production in Clostridium. Nature Communications (2021).
• Engineering Clostridium saccharoperbutylacetonicum for High Level Isopropanol-Butanol-Ethanol (IBE) Production from Acetic Acid Pretreated Switchgrass Using the CRISPR-Cas9 System. ACS Sustainable Chemistry & Engineering (2019).
• Exploiting endogenous CRISPR-Cas system for multiplex genome editing in Clostridium tyrobutyricum and engineer the strain for high-level butanol production. Metabolic Engineering (2018).

Waste valorization and biological resource recovery

We investigate how biological engineering can transform low-value waste streams into value-added products or recover valuable resources from them.

Current research projects

• Rare earth element recovery from acidic wastewaters
  We are developing acid-tolerant microbes and metal-binding proteins to selectively recover rare earth elements from acidic mining and industrial wastewaters. This DOE ARPA-E-supported project connects protein and microbial engineering with practical resource-recovery processes. Read the REE recovery news release.
• Carbon utilization through the NSF CURB Engineering Research Center
  As part of the NSF CURB Engineering Research Center, we engineer non-model microbial hosts to upgrade carbon dioxide-derived intermediates into useful biochemicals, connecting microbial engineering with manufacturing decarbonization. Read the CURB news release.
• Methane-derived bioplastics with Mango Materials
  In collaboration with Mango Materials, we develop genome-engineering tools for methanotrophs and design strains to make methane-derived polyhydroxyalkanoate (PHA) bioplastics easier to recover after fermentation. The project connects strain design with downstream processing and industrial evaluation. Read the Mango Materials news release.

Relevant publications

• Metabolically engineer Clostridium saccharoperbutylacetonicum for comprehensive conversion of acid whey into valuable biofuels and biochemicals. Bioresource Technology (2024).
• Co-valorization of paper mill sludge and corn steep liquor for enhanced n-butanol production with Clostridium tyrobutyricum Δcat1::adhE2. Bioresource Technology (2020).
• Towards comprehensive lignocellulosic biomass utilization for bioenergy production: Efficient biobutanol production from acetic acid pretreated switchgrass with Clostridium saccharoperbutylacetonicum N1-4. Applied Energy (2019).
• Effects of end products on fermentation profiles in Clostridium carboxidivorans P7 for syngas fermentation. Bioresource Technology (2016).

Biological engineering for agriculture, environment, and health

We apply microbial engineering to address challenges in sustainable agriculture, environmental protection, and human health.

Our work includes genome engineering of plant-growth-promoting Bacillus, Bradyrhizobium associated with nitrogen fixation and plant drought tolerance, and aquaculture-associated pathogenic bacteria. Current projects explore microbial approaches to controlling disease in strawberries, enhancing plant growth and stress tolerance, and converting agricultural residues into feed additives to support swine and cattle health and reduce methane emissions from cattle.

We also develop genome-engineering tools and investigate infection mechanisms in human pathogens, including Clostridium difficile. These studies connect fundamental microbial biology with longer-term opportunities to improve disease management and human health.

Relevant publications

• Contributions of hemolytic proteins in virulent Aeromonas hydrophila to motile Aeromonas septicemia disease of channel catfish (Ictalurus punctatus). FEMS Microbiology Letters (2025).
• Targeted Genome Editing of the ACC Deaminase Gene in Bradyrhizobium: Toward Enhanced Plant Growth and Stress Tolerance. Biotechnology and Bioengineering (2025).
• High-Efficiency CRISPR-Cas9 Genome Editing Unveils Biofilm Insights and Enhances Antimicrobial Activity in Bacillus velezensis FZB42. Biotechnology and Bioengineering (2025).
• High-Efficiency Genome Editing in Naturally Isolated Aeromonas hydrophila and Edwardsiella piscicida Using the CRISPR-Cas9 System. Biotechnology and Bioengineering (2025).
• Multiplexed CRISPR-Cpf1-Mediated Genome Editing in Clostridium difficile toward the Understanding of Pathogenesis of C. difficile Infection. ACS Synthetic Biology (2018).
• Genome engineering of Clostridium difficile using the CRISPR-Cas9 system. Clinical Microbiology and Infection (2018).

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