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Chemical Engineering Research Seminar
Prof. Shishir P. S. Chundawat
Department of Chemical and Biochemical Engineering
Rutgers, The State University of New Jersey
Abstract
Carbohydrates (or glycans) are the most abundant class of biomolecules on the planet that are known to play critical metabolic, structural, and functional roles in all biological systems. Given the dense coating of diverse glycan molecules on essentially all cell membrane (e.g., O-linked glycoconjugates displayed on the glycocalyx of mammalian cells or polysaccharides embedded within plant cell walls) and biomolecule surfaces (e.g., N-linked glycoproteins), it is not surprising that glycans play a critical role in cell biology such as mediating interfacial interactions of host cells with infectious or symbiotic agents (e.g., bacteria, viruses), drugs, antibodies, hormones, enzymes, and intercellular signaling receptors amongst numerous other functions. But we are still far from elucidating the role of glycans in the design, engineering, and regulation of biological systems spanning from the molecular to organismal level, unlike other fields like genomics and proteomics. The role of glycans in living systems can be better understood by creating robust biotechnology and analytical toolkits that can uncover the sweet rules of life governing the biosynthesis, organization, and ultimately deconstruction of these complex biomolecules.
The Chundawat Research Group is developing advanced protein and glycan engineering (or broadly glycoengineering) toolkits along with applying novel bioprocessing and biophysical techniques to address fundamental scientific and engineering problems relevant to healthcare, bioenergy, and biomaterials research. Here, the speaker will highlight key advances being made in the broader areas of glycoengineering and biomanufacturing using Carbohydrate-Active enZymes (CAZymes) at Rutgers University. He will specifically highlight some novel strategies being developed in his group using engineered CAZymes for chemoenzymatic synthesis of designer oligosaccharides as prebiotics/antibiotics, autonomous N-linked glycoproteins characterization for enabling continuous biological drugs manufacturing, single-molecule imaging and visualization of how CAZymes/cells assemble and deconstruct cell walls, and using supercharged CAZymes for efficient saccharification of waste cellulosic biomass to fermentable sugars for biofuels production.
Hosted by Dr. Rebecca Ong.
References
(1) Gyorgypal et al. Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. Anal. Chem. 2022, 94 (19), 6986–6995. https://doi.org/10.1021/acs.analchem.1c05396.
(2) Nemmaru et al. Supercharged Cellulases Show Reduced Non-Productive Binding, But Enhanced Activity, on Pretreated Lignocellulosic Biomass. bioRxiv 2021, 2021.10.17.464688. https://doi.org/10.1101/2021.10.17.464688.
(3) Hackl et al. Acoustic Force Spectroscopy Reveals Subtle Differences in Cellulose Unbinding Behavior of Carbohydrate-Binding Modules. Proc. Natl. Acad. Sci. 2022, 119 (42), e2117467119. https://doi.org/10.1073/pnas.2117467119.
(4) Agrawal et al. Click-Chemistry-Based Free Azide versus Azido Sugar Detection Enables Rapid In Vivo Screening of Glycosynthase Activity. ACS Chem. Biol. 2021, 16 (11), 2490–2501. https://doi.org/10.1021/acschembio.1c00585.
(5) Chundawat et al. Molecular Origins of Reduced Activity and Binding Commitment of Processive Cellulases and Associated Carbohydrate-Binding Proteins to Cellulose III. J. Biol. Chem. 2021, 296, 100431. https://doi.org/10.1016/j.jbc.2021.100431.
(6) Bandi et al. Engineered Regulon to Enable Autonomous Azide Ion Biosensing, Recombinant Protein Production, and in Vivo Glycoengineering. ACS Synth. Biol. 2021, 10 (4), 682–689. https://doi.org/10.1021/acssynbio.0c00449.
(7) Bandi et al. Carbohydrate-Active EnZyme (CAZyme) Enabled Glycoengineering for a Sweeter Future. Current Opinion in Biotechnology. December 1, 2020, pp 283–291. https://doi.org/10.1016/j.copbio.2020.09.006.
(8) Bandi et al. Carbohydrate‐binding Domains Facilitate Efficient Oligosaccharides Synthesis by Enhancing Mutant Catalytic Domain Transglycosylation Activity. Biotechnol. Bioeng. 2020, 117, 2944– 2956. https://doi.org/10.1002/bit.27473.
(9) Whitehead et al. Negatively Supercharging Cellulases Render Them Lignin-Resistant. ACS Sustain. Chem. Eng. 2017, 5 (7), 6247–6252. https://doi.org/10.1021/acssuschemeng.7b01202.
(10) Brady et al. Cellobiohydrolase 1 from Trichoderma Reesei Degrades Cellulose in Single Cellobiose Steps. Nat. Commun. 2015, 6, 10149. https://doi.org/10.1038/ncomms10149.
Bio
Dr. Chundawat is a tenured associate professor at the Department of Chemical and Biochemical Engineering at Rutgers University (New Jersey, USA). He has 18 years of multidisciplinary expertise working with carbohydrate-active enzymes (CAZymes); protein modeling and engineering; carbohydrate chemistry; biomanufacturing; and developing novel analytical techniques for characterization of glycans and protein/CAZymes-glycan interactions. He received his BTech in Chemical Technology from the Institute of Chemical Technology (Mumbai, India) in 2004 and his PhD in Chemical Engineering from Michigan State University (East Lansing, Michigan, USA) in 2009. He held a postdoctoral staff scientist position at the Great Lakes Bioenergy Research Center from 2009-2011 and at the University of Wisconsin Madison (Department of Biochemistry, Wisconsin, USA) from 2012-2014. He also held a joint adjunct/research assistant professor position at the Department of Chemical Engineering and Materials Science at Michigan State University before joining Rutgers University in January 2015.
The Chundawat Research Group at Rutgers University takes a carbohydrate or glycan-centric approach to sustainably address relevant problems in the broad areas of bioenergy, biopharmaceutical, biomedical, biomaterials, and bioseparations engineering. His group develops and applies protein and glycan engineering (or glycoengineering), bioprocessing, and biophysical techniques to address fundamental engineering problems centered on carbohydrates. Chundawat’s research team at Rutgers is actively working towards expanding the repertoire of applications for carbohydrate-active enzymes and glycans in general in the area of biomanufacturing and human health, in particular. He has served (or is currently serving) as a Principal Investigator (PI) on several National Science Foundation, Department of Energy, and Food and Drug Administration (FDA) funded research grants, including the 2019 National Science Foundation (NSF) Early Career Award focused on development of novel process analytical technology (PAT) toolkit for the single-molecule characterization of protein-glycan biophysical interactions and the recent 2022 National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) award to develop integrated bioprocess PAT for real-time monitoring of biologics N-glycosylation. He is currently Rutgers PI for several industry and federally funded projects focused on establishment of a new biopharmaceutical engineering program at Rutgers and in particular development of suitable at-line/on-line PAT for improved continuous manufacturing of biological-based drugs like glycosylated monoclonal antibodies. He is the recipient of the 2022 A. Walter Tyson Endowment Award, 2020 Agilent Award, 2019 National Science Foundation (NSF) Career Award, 2018 A. Walter Tyson Assistant Professorship Award, and 2016 Ralph E. Powe Junior Faculty Award among some of his academic honors at Rutgers University.
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