Biocatalysis & Biomanufacturing

We are using biocatalysis in production of animal-free glycosaminoglycans (GAGs), including the world’s highest volume anticoagulant, heparin. We are also using biocatalysis in energy-related research, with a focus on designing metabolic pathways using cell-free metabolic pathway engineering coupled with electrochemical bioreactors and use of enzymes to regenerate NAD(P)+ from inhibitory NAD(P)H isomers. Finally, we are using cell-free pathway engineering to generate various (bio)chemicals with high efficiency.

Projects

Glycosaminoglycans (GAGs) are critical components of the stem cell niche and consist of long chain polymers of recurring disaccharide units usually composed of either D-glucosamine or D-galactosamine, and D-glucuronic acid or L-iduronic acid that when coupled to a core protein result in the formation of proteoglycans (PGs). We have developed the first animal-free biomanufacturing process to generate the critical anticoagulant drug heparin.

The use of in vivo synthetic biology has seen remarkable efforts in the greener production of chemicals and compounds at a commercial scale. However, such systems tend to be limited in their productivities. We are interested in developing yet more efficient platforms for biomanufacturing.  L-malic acid, a compound with significant applications in food, pharmaceutical, and chemical industries, represents an excellent target for innovative biomanufacturing strategies.

Nearly 20% of known oxidoreductases require cofactors to supply stoichiometric quantities of reducing equivalents. For the majority of these oxidoreductases, NAD(P)H is the required cofactor. Since the total pool of intracellular NAD(P)H and NAD(P)+ is relatively small, cofactor recycling is needed in the order of thousands to millions of cycles. We are developing an electrochemical bioreactor (EBR) for enzymatic transformations and ultimately leading to fermentation-based biotransformations.
There is growing interest in developing new tools and technologies to improve and expand the use of gene therapy as a potential treatment for several genetic and degenerative diseases. Viral vectors, In particular, lentiviral vectors (LVVs) are of interest because of their ability to infect both dividing and non-dividing cells, as well as for their capacity to carry a large genetic payload size. This makes LVVs ideal delivery candidates for gene and CAR-T therapies. We are developing new approaches for the rapid optimization of LVV production and characterization, which will improve opportunities for LVV manufacturing and use in gene therapy applications.
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