Biomolecular Engineering of Antibacterial and Antiviral Agents

We are exploiting nature’s biocatalytic defense mechanisms to combat microbial and viral infections, overcome bacterial resistance mechanisms, and applying our approach to surfaces within common infrastructures, including hospitals, schools, food processing facilities, etc. Our approach involves two classes of enzymes; peptidoglycan hydrolases and oxidative biocatalysts. The former are lytic enzymes, which are extremely selective and do not require reagents apart from water to act. The oxidative enzymes, including oxidases, peroxidases and perhydrolases, are generally nonselective and require addition of reagents to catalyze their microbicidal activity. In both classes, these enzymes can be used in their soluble form or embedded into materials that can be used to coat surfaces and kill bacteria on contact. We are also developing various routes to novel antivirals, including broad-based coronavirus inactivation based on perhydrolases and sulfated polysaccharides.


Broad-spectrum antibiotics indiscriminately kill bacteria, removing non-pathogenic microorganisms and leading to evolution of antibiotic resistant strains. Specific antimicrobials that could selectively kill pathogenic bacteria without targeting other bacteria in the natural microbial community or microbiome may be able to address this concern.
The lytic enzymes that target Gram-positive bacteria nearly universally have a two-domain structure, with the N-terminal catalytic domain bound through a short linker to a cell wall binding domain. We have exploited this modularity in designing new enzyme systems.
Recovery of recombinant proteins and plasmids from E. coli cytoplasm depends on cell disruption by mechanical, chemical, and/or enzymatic methods, which usually cause incomplete cell breakage or protein denaturation. We have designed controllable autolytic E. coli strains to facilitate purification of recombinant proteins and plasmid DNA that is based on a programmable autolytic E. coli.
In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA).
Perhydrolase-polydopamine composite coatings possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing.
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